U.S. patent number 6,238,678 [Application Number 09/039,750] was granted by the patent office on 2001-05-29 for methods of regulating skin appearance with vitamin b3 compound.
This patent grant is currently assigned to The Procter & Gamble Company. Invention is credited to Kimberly Ann Biedermann, Donald Lynn Bissett, John Erich Oblong.
United States Patent |
6,238,678 |
Oblong , et al. |
May 29, 2001 |
Methods of regulating skin appearance with vitamin B3 compound
Abstract
The present invention relates to topical compositions comprising
a vitamin B.sub.3 compound which are useful for regulating skin
condition, especially for regulating the signs of skin aging.
Inventors: |
Oblong; John Erich (Cincinnati,
OH), Bissett; Donald Lynn (Hamilton, OH), Biedermann;
Kimberly Ann (Cincinnati, OH) |
Assignee: |
The Procter & Gamble
Company (Cincinnati, OH)
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Family
ID: |
46255927 |
Appl.
No.: |
09/039,750 |
Filed: |
March 16, 1998 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
|
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834010 |
Apr 11, 1997 |
5939082 |
|
|
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554067 |
Nov 6, 1995 |
5833998 |
|
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Current U.S.
Class: |
424/401; 514/944;
424/70.1; 514/458; 514/844; 514/887; 514/847; 514/725; 514/356 |
Current CPC
Class: |
A61K
8/673 (20130101); A61K 8/9789 (20170801); A61K
8/675 (20130101); A61Q 19/00 (20130101); A61K
8/671 (20130101); A61K 8/42 (20130101); A61K
8/63 (20130101); A61Q 19/10 (20130101); A61K
8/9794 (20170801); Y10S 514/887 (20130101); Y10S
514/847 (20130101); A61Q 5/02 (20130101); A61Q
5/12 (20130101); A61Q 19/08 (20130101); A61Q
1/02 (20130101); Y10S 514/844 (20130101); Y10S
514/944 (20130101) |
Current International
Class: |
A61Q
5/02 (20060101); A61Q 19/10 (20060101); A61Q
1/02 (20060101); A61Q 19/00 (20060101); A61Q
19/08 (20060101); A61Q 5/12 (20060101); A61K
8/42 (20060101); A61K 8/30 (20060101); A61K
8/63 (20060101); A61K 8/67 (20060101); A61K
8/97 (20060101); A61K 8/96 (20060101); A61K
006/00 (); A61K 007/00 () |
Field of
Search: |
;424/401,70.1
;514/844,845,846,938,847,887,356,458,725,944 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
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Other References
Tay et al., "Stimulation of Collagen Type I and Type II mRNA
Synthesis in Human Skin Fibroblasts by Nicotinamide", Clinical
Research, vol. 39, No. 1, 1991. .
Commercial Product Information: Chanel Complexe Intensif Night Lift
Cream. .
Commercial Product Information: Chanel Creme Parfaite Night Lift
Plus Multi-Hydroxy. .
Article: "Effects of Niacinamide on Ceramide Biosynthesis and
Differentiation of Cultured Human Keratinocytes" Osamu Tanno, et
al. Basic Research Laboratory, Kanebo Ltd., 3.sup.rd ASCS
Conference, Taipei, Taiwan, 1997. .
Abstract--Accession Number: 97-285134 [26] (Japan) A61K:031-355 (No
translation)..
|
Primary Examiner: Page; Thurman K.
Assistant Examiner: Nola-Baron; Liliana Di
Attorney, Agent or Firm: Matthews; Armina E. Tsuneki;
Fumiko
Parent Case Text
CROSS REFERENCE
This application is a continuation-in-part of U.S. application Ser.
No. 08/834,010, filed Apr. 11, 1997 now U.S. Pat. No 5,939,082,
which is a continuation-in-part of U.S. application Ser. No.
08/554,067, filed Nov. 6, 1995 U.S. Pat. No. 5,833,998. U.S.
application Ser. No. 08/834,010, in turn, claims priority under
Title 35, United States Code 119(e) from Provisional application
Ser. No. 60/016,043, filed Apr. 23, 1996, Provisional Application
Ser. No. 60/025,242, filed Sep. 16, 1996, and Provisional
application Ser. No. 60/028,902, filed Oct. 21, 1996.
Claims
What is claimed is:
1. A topical composition for regulating skin condition, comprising
a safe and effective amount, ranging from about 2% to about 5%, of
a vitamin B.sub.3 compound selected from the group consisting of
niacinamide, tocopherol nicotinate, and mixtures thereof, from
about 0.01% to about 2% of retinyl propionate, from about 0.1% to
about 10% of an anti-oxidant selected from the group consisting of
tocopherol, esters of tocopherol, and combinations thereof, from
about 0.1 to about 20% of a moisturizing agent selected from the
group consisting of panthenol, pantothenic acid derivatives,
glycerin, glycerol, and mixtures thereof, and a carrier for said
vitamin B.sub.3 compound, said anti-oxidant, said moisturizing
agent, and said retinyl propionate.
2. The composition of claim 1 wherein said vitamin B.sub.3 compound
is niacinamide, said anti-oxidant is tocopherol acetate, and said
moisturizing agent is panthenol.
3. A skin moisturizing composition, comprising:
(a) from about 0.01% to about 50% of a vitamin B.sub.3 compound,
selected from the group consisting of niacinamide, tocopherol
nicotinate, and mixtures thereof;
(b) from about 0.1% to about 20% of a moisturizing agent selected
from the group consisting of guanidine, sucrose polyesters of fatty
acids, urea, pyrrolidone carboxylic acid, panthenol, pantothenic
acid, petrolatum, glycerol, glycerol monopropoxylate, butanetriol,
hexanetriol, butylene glycol, hexylene glycol, isononyl
isononanate, isohexadecane, methyl isostearate, ethyl isostearate,
cetyl ricinoleate and mixtures thereof;
(c) a second active ingredient selected from the group consisting
of deoxy-arbutin, thio-deoxy-arbutin, tocopherol acetate,
tocopherol sorbate, iron chelators, plant polyphenols, ibuprofen,
naproxen, flufenamic acid, etofenamate, aspirin, hydrocortisone and
mixtures thereof;
(d) from 0.1% to about 2% of retinyl propionate; and
(e) a carrier for said vitamin B.sub.3 compound, said moisturizing
agent, said second active, and said retinyl propionate.
4. A composition according to claim 3, wherein the vitamin is B3
compound is tocopherol nicotinate.
5. A composition according to claim 3, wherein the moisturizing
agent is selected from the group consisting of guanidine, sucrose
polyesters of fatty acids, urea, panthenol, petrolatum, glycerol,
butylene glycol, isononyl isononanate, isohexadecane, methyl
isostearate, ethyl isostearate, cetyl ricinoleate and mixtures
thereof.
6. A composition according to claim 3, wherein the vitamin B3
compound is niacinamide, the second active is tocopherol acetate,
and the moisturizing agent is panthenol.
7. A composition according to claim 3, wherein the second active is
tocopherol acetate, and the moisturizing agent is panthenol.
Description
TECHNICAL FIELD
The present invention relates to topical compositions containing a
vitamin B.sub.3 compound for regulating the condition of skin,
especially for regulating visible and/or tactile discontinuities in
skin associated, e.g., with skin aging. Preferred compositions
contain niacinamide.
BACKGROUND OF THE INVENTION
Many personal care products currently available to consumers are
directed primarily to improving the health and/or physical
appearance of the skin. Among these skin care products, many are
directed to delaying, minimizing or even eliminating skin wrinkling
and other histological changes typically associated with the aging
of skin or environmental damage to human skin.
Skin is subject to insults by many extrinsic and intrinsic factors.
Extrinsic factors include ultraviolet radiation (e.g., from sun
exposure), environmental pollution, wind, heat, low humidity, harsh
surfactants, abrasives, and the like. Intrinsic factors include
chronological aging and other biochemical changes from within the
skin. Whether extrinsic or intrinsic, these factors result in
visible signs of skin aging and environmental damage, such as
wrinkling and other forms of roughness (including increased pore
size, flaking and skin lines), and other histological changes
associated with skin aging or damage. To many people, skin wrinkles
are a reminder of the disappearance of youth. As a result, the
elimination of wrinkles has become a booming business in
youth-conscious societies. Treatments range from cosmetic creams
and moisturizers to various forms of cosmetic surgery.
Extrinsic or intrinsic factors may result in the thinning and
general degradation of the skin. For example, as the skin naturally
ages, there is a reduction in the cells and blood vessels that
supply the skin. There is also a flattening of the dermal-epidermal
junction which results in weaker mechanical resistance of this
junction. See, for example, Oikarinen, "The Aging of Skin:
Chronoaging Versus Photoaging," Photodermatol. Photoimmunol.
Photomed., vol. 7, pp. 3-4, 1990, which is incorporated by
reference herein in its entirety.
It has now been found that vitamin B.sub.3 compounds, including
niacinamide, provide benefits in regulating skin condition
previously unrecognized in the art of which the present inventors
are aware. For example, topical niacinamide can regulate the signs
of skin aging, e.g., reduce or efface the visibility of the fine
lines, wrinkles, and other forms of uneven or rough surface texture
associated with aged or photo damaged skin. It has also now been
found that topical compositions containing a vitamin B.sub.3
compound and a retinoid provide benefits in regulating skin
condition previously unrecognized in the art of which the present
inventors are aware. For example, such compositions enable the
regulation of signs of skin aging with decreased potential for
retinoid dermatitis. In addition, the vitamin B.sub.3 compound in
combination with certain retinoids synergistically regulates signs
of skin aging, especially visible and/or tactile discontinuities in
skin texture associated with aged skin, including fine lines and
wrinkles.
It is therefore an object of the present invention to provide
topical compositions for prophylactically and/or therapeutically
regulating mammalian skin condition (especially of human skin, more
especially facial skin), containing a vitamin B.sub.3 compound,
especially niacinamide.
It is another object of the present invention to provide topical
compositions for prophylactically and/or therapeutically regulating
signs of mammalian skin aging, containing a vitamin B.sub.3
compound, especially niacinamide.
It is another object of the present invention to provide topical
compositions for prophylactically and/or therapeutically regulating
visible and/or tactile discontinuities in mammalian skin texture,
including fine lines, wrinkles, enlarged pores, roughness, dryness
and other skin texture discontinuities associated with aged skin,
containing a vitamin B.sub.3 compound, especially niacinamide.
It is another object of the present invention to provide topical
compositions for skin moisturization, photoprotection and skin
lightening comprising a vitamin B3 compound and a second
pharmaceutical active.
Other objects of the present invention are to provide such topical
compositions further comprising a retinoid.
The present invention also relates to methods of providing such
regulation using the subject compositions.
The present invention further relates to methods of providing skin
moisturization, photoprotection and skin lightening.
These and other objects of this invention will become apparent in
light of the following disclosure.
SUMMARY OF THE INVENTION
The present invention relates to regulation of skin condition
involving the topical application of a composition containing a
vitamin B.sub.3 compound, especially niacinamide. The present
invention also relates to regulation of skin condition involving
topical application of a composition containing a vitamin B.sub.3
compound, especially niacinamide, and a retinoid. The invention
especially relates to regulation of signs of skin aging, more
especially regulating visible and/or tactile discontinuities in
mammalian skin texture, including discontinuities associated with
aged skin, involving the topical application of such compositions.
The present invention relates to both prophylactic and therapeutic
regulation of skin condition.
In preferred embodiments, the vitamin B.sub.3 compound is
substantially free of the salt form and is uncomplexed, the vitamin
B.sub.3 compound is niacinamide, and the carrier contains a
hydrophilic diluent.
DETAILED DESCRIPTION OF THE INVENTION
All percentages and ratios used herein are by weight of the total
composition and all measurements made are at 25.degree. C., unless
otherwise designated.
The compositions of the present invention can comprise, consist
essentially of, or consist of, the essential as well as optional
ingredients and components described herein. As used herein,
"consisting essentially of" means that the composition or component
may include additional ingredients, but only if the additional
ingredients do not materially alter the basic and novel
characteristics of the claimed compositions or methods.
All publications cited herein are hereby incorporated by reference
in their entirety.
The term "topical application", as used herein, means to apply or
spread the compositions of the present invention onto the surface
of the skin.
The term "dermatologically-acceptable," as used herein, means that
the compositions or components thereof so described are suitable
for use in contact with human skin without undue toxicity,
incompatibility, instability, allergic response, and the like.
The term "safe and effective amount" as used herein means an amount
of a compound or composition sufficient to significantly induce a
positive benefit, preferably a positive skin appearance or feel
benefit, including independently the benefits disclosed herein, but
low enough to avoid serious side effects, i.e., to provide a
reasonable benefit to risk ratio, within the scope of sound
judgment of the skilled artisan.
The compositions of the present invention are useful for topical
application and for regulating skin condition, including visible
and/or tactile discontinuities in skin (especially the skin
surface; such discontinuities are generally undesired). Such
discontinuities may be induced or caused by internal and/or
external factors, and include the signs of skin aging described
herein. "Regulating skin condition" includes prophylactically
regulating and/or therapeutically regulating skin condition,
including visible and/or tactile discontinuities in skin. As used
herein, prophylactically regulating skin condition includes
delaying, minimizing and/or preventing visible and/or tactile
discontinuities in skin. As used herein, therapeutically regulating
skin condition includes ameliorating, e.g., diminishing, minimizing
and/or effacing, discontinuities in skin. Regulating skin condition
involves improving skin appearance and/or feel.
The compositions of the present invention are useful for regulating
signs of skin aging, more especially visible and/or tactile
discontinuities in skin texture associated with aging. "Regulating
the signs of skin aging" includes prophylactically regulating
and/or therapeutically regulating one or more of such signs
(similarly, regulating a given sign of skin aging, e.g., lines,
wrinkles or pores, includes prophylactically regulating and/or
therapeutically regulating that sign). As used herein,
prophylactically regulating such signs includes delaying,
minimizing and/or preventing signs of skin aging. As used herein,
therapeutically regulating such signs includes ameliorating, e.g.,
diminishing, minimizing and/or effacing signs of skin aging. "Signs
of skin aging" include, but are not limited to, all outward visibly
and tactilely perceptible manifestations as well as any other macro
or micro effects due to skin aging. Such signs may be induced or
caused by intrinsic factors or extrinsic factors, e.g.,
chronological aging and/or environmental damage. These signs may
result from processes which include, but are not limited to, the
development of textural discontinuities such as wrinkles, including
both fine superficial wrinkles and coarse deep wrinkles, skin
lines, crevices, bumps, large pores (e.g., associated with adnexal
structures such as sweat gland ducts, sebaceous glands, or hair
follicles), scaliness, flakiness and/or other forms of skin
unevenness or roughness, loss of skin elasticity (loss and/or
inactivation of functional skin elastin), sagging (including
puffiness in the eye area and jowls), loss of skin firmness, loss
of skin tightness, loss of skin recoil from deformation,
discoloration (including undereye circles), blotching, sallowness,
hyperpigmented skin regions such as age spots and freckles,
keratoses, abnormal differentiation, hyperkeratinization,
elastosis, collagen breakdown and other histological changes in the
stratum corneum, dermis, epidermis, the skin vascular system (e.g.,
telangiectasia or spider vessels), and underlying tissues,
especially those proximate to the skin.
It is to be understood that the present invention is not to be
limited to regulation of the above mentioned "signs of skin aging"
which arise due to mechanisms associated with skin aging, but is
intended to include regulation of said signs irrespective of the
mechanism of origin. As used herein, "regulating skin condition" is
intended to include regulation of such signs irrespective of the
mechanism of origin.
The present invention is especially useful for therapeutically
regulating visible and/or tactile discontinuities in mammalian skin
texture, including texture discontinuities associated with skin
aging. As used herein, therapeutically regulating such
discontinuities includes ameliorating, e.g., diminishing,
minimizing and/or effacing visible and/or tactile discontinuities
in the texture of mammalian skin, to thereby provide improved skin
appearance and/or feel, e.g., a smoother, more even appearance
and/or feel. Such visible and/or tactile discontinuities in skin
texture include crevices, bumps, pores, fine lines, wrinkles,
scales, flakes and/or other forms of textural unevenness or
roughness associated with skin aging. For example, the length,
depth, and/or other dimension of lines and/or wrinkles are
decreased, the apparent diameter of pores decreases, or the
apparent height of tissue immediately proximate to pore openings
approaches that of the interadnexal skin.
The present invention is also especially usefull for
prophylactically regulating visible and/or tactile discontinuities
in mammalian skin texture, including texture discontinuities
associated with skin aging. As used herein, prophylactically
regulating such discontinuities includes delaying, minimizing
and/or preventing visible and/or tactile discontinuities in the
texture of mammalian skin, to thereby provide improved skin
appearance and/or feel, e.g., a smoother, more even appearance
and/or feel.
The compositions of the present invention are also useful for
promoting exfoliation of the skin. Without intending to be bound or
limited by theory, it is believed that the compositions containing
the vitamin B.sub.3 compound, particularly niacinamide, strengthen
the energy state of cells regulating exfoliation, resulting in
normalization of epidermal differentiation and keratinization.
The compositions of the present invention are still further useful
for moisturizing the skin. Without intending to be bound or limited
by theory, it is believed that the compositions containing the
vitamin B.sub.3 compound, particularly niacinamide and/or
tocopherol nicotinate, increase skin moisturization or hydration by
several different mechanisms. One mechanism involves the effect of
vitamin B.sub.3 compounds on natural moisturizing factors. Natural
moisturizing factors include the water-binding, metabolic
by-products of skin proteins, especially filaggrin. It is believed
that vitamin B.sub.3 compounds increase the level of the above
mentioned skin proteins, thereby increasing the level of natural
moisturizing factors and, thus, moisturization. Another mechanism
involves the effect of vitamin B.sub.3 compounds on the level
and/or molecular weight of keratin proteins in the stratum corneum.
These proteins bind water and aid in providing flexibility to the
corneum cell layer. Increased keratin level, thus, increases the
concentration of moisture-binding proteins, resulting in improved
skin moisturization. The degree of skin moisturization attained or
stratum corneum flexibility achieved as a result of hydration is
also related to the type of keratin present Mature stratum corneum
cell layers contain keratin proteins of higher molecular weight
than those found in the viable epidermal cell layers. These higher
molecular weight keratins (e.g., keratins having a molecular weight
of about 67,000) tend to bind more water and/or provide greater
stratum corneum flexibility. It is believed that Vitamin B.sub.3
compounds stimulate production of these higher molecular weight
keratin. A third mechanism involves the effect of Vitamin B.sub.3
compounds on the level of involucrin and desmosomal proteins.
Involucrin is a protein precursor to the stratum corneum cell
envelop which encases the keratin proteins and natural moisturizing
factors. Desmosomal proteins are in close association with the
stratum corneum cell envelop and aid in connecting the stratum
corneum cells. Vitamin B.sub.3 compounds increase the level of
involucrin and desmosomal proteins. Increased involucrin and the
desmosomal protein levels augment and strengthen the corneum cell
envelope, helping to retard the dehydration of the encased keratins
and natural moisturizing factors and, thereby, improving skin
moisturization.
Vitamin B.sub.3 Component
The compositions of the present invention comprise a safe and
effective amount of a vitamin B.sub.3 compound. The compositions of
the present invention preferably comprise from about 0.01% to about
50%, more preferably from about 0.1% to about 10%, even more
preferably from about 0.5% to about 10%, and still more preferably
from about 1% to about 5%, most preferably from about 2% to about
5%, of the vitamin B.sub.3 compound.
As used herein, "vitamin B.sub.3 compound" means a compound having
the formula: ##STR1##
wherein R is --CONH.sub.2 (i.e., niacinamide), --COOH (i.e.,
nicotinic acid) or --CH.sub.2 OH (i.e., nicotinyl alcohol);
derivatives thereof, and salts of any of the foregoing.
Exemplary derivatives of the foregoing vitamin B.sub.3 compounds
include nicotinic acid esters, including non-vasodilating esters of
nicotinic acid, nicotinyl amino acids, nicotinyl alcohol esters of
carboxylic acids, nicotinic acid N-oxide and niacinamide
N-oxide.
Suitable esters of nicotinic acid include nicotinic acid esters of
C.sub.1 -C.sub.22, preferably C.sub.1 -C.sub.16, more preferably
C.sub.1 -C.sub.6 alcohols. The alcohols are suitably straight-chain
or branched chain, cyclic or acyclic, saturated or unsaturated
(including aromatic), and substituted or unsubstituted. The esters
are preferably non-vasodilating. As used herein, "non-vasodilating"
means that the ester does not commonly yield a visible flushing
response after application to the skin in the subject compositions
(the majority of the general population would not experience a
visible flushing response, although such compounds may cause
vasodilation not visible to the naked eye). Alternatively, a
nicotinic acid material which is rubifacient at higher doses could
be used at a lower dose to reduce or eliminate the rubifacient
effect. Non-vasodilating esters of nicotinic acid include
tocopherol nicotinate and inositol hexanicotinate; tocopherol
nicotinate is preferred.
Other derivatives of the vitamin B.sub.3 compound are derivatives
of niacinamide resulting from substitution of one or more of the
amide group hydrogens. Nonlimiting examples of derivatives of
niacinamide useful herein include nicotinyl amino acids, derived,
for example, from the reaction of an activated nicotinic acid
compound (e.g., nicotinic acid azide or nicotinyl chloride) with an
amino acid, and nicotinyl alcohol esters of organic carboxylic
acids (e.g., C1-C18). Specific examples of such derivatives include
nicotinuric acid (C.sub.8 H.sub.8 N.sub.2 O.sub.3) and nicotinyl
hydroxamic acid (C.sub.6 H.sub.6 N.sub.2 O.sub.2), which have the
following chemical structures: nicotinuric acid: ##STR2##
nicotinyl hydroxamic acid: ##STR3##
Exemplary nicotinyl alcohol esters include nicotinyl alcohol esters
of the carboxylic acids salicylic acid, acetic acid, glycolic acid,
palmitic acid and the like. Other non-limiting examples of vitamin
B.sub.3 compounds useful herein are 2-chloronicotinamide,
6-aminonicotinamide, 6-methylnicotinamide, n-methylnicotinamide,
n,n-diethylnicotinamide, n-(hydroxymethyl)-nicotinamide, quinolinic
acid imide, nicotinanilide, n-benzylnicotinamide,
n-ethylnicotinamide, nifenazone, nicotinaldehyde, isonicotinic
acid, methyl isonicotinic acid, thionicotinamide, nialamide,
1-(3-pyridylmethyl) urea, 2-mercaptonicotinic acid, nicomol, and
niaprazine.
Examples of the above vitamin B.sub.3 compounds are well known in
the art and are commercially available from a number of sources,
e.g., the Sigma Chemical Company (St. Louis, Mo.); ICN Biomedicals,
Inc. (Irvin, Calif.) and Aldrich Chemical Company (Milwaukee,
Wis.).
One or more vitamin B.sub.3 compounds may be used herein. Preferred
vitamin B.sub.3 compounds are niacinamide and tocopherol
nicotinate. Niacinamide is more preferred.
When used, salts, derivatives, and salt derivatives of niacinamide
are preferably those having substantially the same efficacy as
niacinamide in the methods of regulating skin condition described
herein.
Salts of the vitamin B.sub.3 compound are also useful herein.
Nonlimiting examples of salts of the vitamin B.sub.3 compound
useful herein include organic or inorganic salts, such as inorganic
salts with anionic inorganic species (e.g., chloride, bromide,
iodide, carbonate, preferably chloride), and organic carboxylic
acid salts (including mono-, di- and tri-C1-C18 carboxylic acid
salts, e.g., acetate, salicylate, glycolate, lactate, malate,
citrate, preferably monocarboxylic acid salts such as acetate).
These and other salts of the vitamin B.sub.3 compound can be
readily prepared by the skilled artisan, for example, as described
by W. Wenner, "The Reaction of L-Ascorbic and D-Isoascorbic Acid
with Nicotinic Acid and Its Amide", J. Organic Chemistry, VOL. 14,
22-26 (1949), which is incorporated herein by reference. Wenner
describes the synthesis of the ascorbic acid salt of
niacinamide.
In a preferred embodiment, the ring nitrogen of the vitamin B.sub.3
compound is substantially chemically free (e.g., unbound and/or
unhindered), or after delivery to the skin becomes substantially
chemically free ("chemically free" is hereinafter alternatively
referred to as "uncomplexed"). More preferably, the vitamin B.sub.3
compound is essentially uncomplexed. Therefore, if the composition
contains the vitamin B.sub.3 compound in a salt or otherwise
complexed form, such complex is preferably substantially
reversible, more preferably essentially reversible, upon delivery
of the composition to the skin. For example, such complex should be
substantially reversible at a pH of from about 5.0 to about 6.0.
Such reversibility can be readily determined by one having ordinary
skill in the art.
More preferably the vitamin B.sub.3 compound is substantially
uncomplexed in the composition prior to delivery to the skin.
Exemplary approaches to minimizing or preventing the formation of
undesirable complexes include omission of materials which form
substantially irreversible or other complexes with the vitamin
B.sub.3 compound, pH adjustment, ionic strength adjustment, the use
of surfactants, and formulating wherein the vitamin B.sub.3
compound and materials which complex therewith are in different
phases. Such approaches are well within the level of ordinary skill
in the art.
Thus, in a preferred embodiment, the vitamin B.sub.3 compound
contains a limited amount of the salt form and is more preferably
substantially free of salts of a vitamin B.sub.3 compound.
Preferably the vitamin B.sub.3 compound contains less than about
50% of such salt, and is more preferably essentially free of the
salt form. The vitamin B.sub.3 compound in the compositions hereof
having a pH of from about 4 to about 7 typically contain less than
about 50% of the salt form.
The vitamin B.sub.3 compound may be included as the substantially
pure material, or as an extract obtained by suitable physical
and/or chemical isolation from natural (e.g., plant) sources. The
vitamin B.sub.3 compound is preferably substantially pure, more
preferably essentially pure.
Carrier
The compositions of the present invention comprise a
dermatologically acceptable carrier within which the vitamin
B.sub.3 compound is incorporated to enable the vitamin B.sub.3
compound and optional other actives to be delivered to the skin at
an appropriate concentration. The carrier can thus act as a
diluent, dispersant, solvent, or the like for the active(s) which
ensures that it can be applied to and distributed evenly over the
selected target at an appropriate concentration.
The carrier may contain one or more dermatologically acceptable
solid, semi-solid or liquid fillers, diluents, solvents, extenders
and the like. The carrier may be solid, semi-solid or liquid. The
carrier can itself be inert or it can possess dermatological
benefits of its own. Concentrations of the carrier can vary with
the carrier selected and the intended concentrations of the
essential and optional components.
Suitable carriers include conventional or otherwise known carriers
that are dermatologically acceptable. The carrier should also be
physically and chemically compatible with the essential components
described herein, and should not unduly impair stability, efficacy
or other use benefits associated with the compositions of the
present invention. Preferred components of the compositions of this
invention should be capable of being comingled in a manner such
that there is no interaction which would substantially reduce the
efficacy of the composition under ordinary use situations.
The type of carrier utilized in the present invention depends on
the type of product form desired for the composition. The topical
compositions useful in the subject invention may be made into a
wide variety of product forms such as are known in the art. These
include, but are not limited to, lotions, creams, gels, sticks,
sprays, ointments, pastes, mousses and cosmetics (e.g., solid,
semi-solid, or liquid make-up, including foundations, eye-makeup,
pigmented or non-pigmented lip treatments, e.g., lipsticks, and the
like). These product forms may comprise several types of carriers
including, but not limited to, solutions, aerosols, emulsions,
gels, solids, and liposomes.
Preferred carriers contain a dermatologically acceptable,
hydrophilic diluent. As used herein, "diluent" includes materials
in which the vitamin B.sub.3 compound can be dispersed, dissolved,
or otherwise incorporated. Hydrophilic diluents include water,
organic hydrophilic diluents such as lower monovalent alcohols
(e.g., C.sub.1 -C.sub.4) and low molecular weight glycols and
polyols, including propylene glycol, polyethylene glycol (e.g.,
Molecular Weight 200-600 g/mole), polypropylene glycol (e.g.,
Molecular Weight 425-2025 g/mole), glycerol, butylene glycol,
1,2,4-butanetriol, sorbitol esters, 1,2,6-hexanetriol, ethanol,
isopropanol, sorbitol esters, butanediol, ether propanol,
ethoxylated ethers, propoxylated ethers and combinations thereof.
Water is a preferred diluent. The composition preferably comprises
from about 80% to about 99.99% of the hydrophilic diluent and the
vitamin B.sub.3 compound in the above described amounts.
Solutions according to the subject invention typically include a
dermatologically acceptable hydrophilic diluent. Solutions useful
in the subject invention preferably contain from about 80% to about
99.99% of the hydrophilic diluent and the vitamin B.sub.3 compound
in the above described amounts.
Aerosols according to the subject invention can be formed by adding
a propellant to a solution such as described above. Exemplary
propellants include chloro-fluorinated lower molecular weight
hydrocarbons. Additional propellants that are useful herein are
described in Sagarin, Cosmetics Science and Technology, 2nd
Edition, Vol. 2, pp. 443-465 (1972), incorporated herein by
reference. Aerosols are typically applied to the skin as a spray-on
product.
Preferred carriers comprise an emulsion such as oil-in-water
emulsions, water-in-oil emulsions, and water-in-silicone emulsions.
As will be understood by the skilled artisan, a given component
will distribute primarily into either the water or oil/silicone
phase, depending on the water solubility/dispersibility of the
component in the composition. Preferred vitamin B.sub.3 compounds
distribute primarily into the aqueous phase. Oil-in-water emulsions
are especially preferred.
Emulsions according to the present invention generally contain a
solution as described above and a lipid or oil. Lipids and oils may
be derived from animals, plants, or petroleum and may be natural or
synthetic (i.e., man-made). Preferred emulsions also contain a
humectant, such as glycerin. Emulsions will preferably further
contain from about 1% to about 10%, more preferably from about 2%
to about 5%, of an emulsifier, based on the weight of the carrier.
Emulsifiers may be nonionic, anionic or cationic. Suitable
emulsifiers are disclosed in, for example, U.S. Pat. No. 3,755,560,
issued Aug. 28, 1973, Dickert et al.; U.S. Pat. No. 4,421,769,
issued Dec. 20, 1983, Dixon et al.; and McCutcheon's Detergents and
Emulsifiers, North American Edition, pages 317-324 (1986), each
incorporated herein by reference.
The emulsion may also contain an anti-foaming agent to minimize
foaming upon application to the skin. Anti-foaming agents include
high molecular weight silicones and other materials well known in
the art for such use.
Suitable emulsions may have a wide range of viscosities, depending
on the desired product form. Exemplary low viscosity emulsions,
which are preferred, have a viscosity of about 50 centistokes or
less, more preferably about 10 centistokes or less, most preferably
about 5 centistokes or less.
Preferred water-in-silicone and oil-in-water emulsions are
described in greater detail below.
a) Water-in-silicone Emulsion
Water-in-silicone emulsions contain a continuous silicone phase and
a dispersed aqueous phase.
(i) Continuous Silicone Phase
Preferred water-in-silicone emulsions of the present invention
comprise from about 1% to about 60%, preferably from about 5% to
about 40%, more preferably from about 10% to about 20%, by weight
of a continuous silicone phase. The continuous silicone phase
exists as an external phase that contains or surrounds the
discontinuous aqueous phase described hereinafter.
The continuous silicone phase contains a polyorganosiloxane oil. A
preferred water-in-silicone emulsion system is formulated to
provide an oxidatively stable vehicle for the optional retinoid.
The continuous silicone phase of these preferred emulsions
comprises between about 50% and about 99.9% by weight of
organopolysiloxane oil and less than about 50% by weight of a
non-silicone oil. In an especially preferred embodiment, the
continuous silicone phase comprises at least about 50%, preferably
from about 60% to about 99.9%, more preferably from about 70% to
about 99.9%, and even more preferably from about 80% to about
99.9%, polyorganosiloxane oil by weight of the continuous silicone
phase, and up to about 50% non-silicone oils, preferably less about
40%, more preferably less than about 30%, even more preferably less
than about 10%, and most preferably less than about 2%, by weight
of the continuous silicone phase. These preferred emulsion systems
provide more oxidative stability to the retinoid over extended
periods of time than comparable water-in-oil emulsions containing
lower concentrations of the polyorganosiloxane oil. Concentrations
of non-silicone oils in the continuous silicone phase are minimized
or avoided altogether so as to further enhance oxidative stability
of the selected retinoid in the compositions. Water-in-silicone
emulsions of this type are described in copending U.S. patent
application Ser. No. 08/570,275, filed Dec. 11, 1995, in the names
of Joseph Michael Zukowski, Brent William Mason, Larry Richard
Robinson and Greg George Hillebrand, incorporated herein by
reference.
The organopolysiloxane oil for use in the composition may be
volatile, non-volatile, or a mixture of volatile and non-volatile
silicones. The term "nonvolatile" as used in this context refers to
those silicones that are liquid under ambient conditions and have a
flash point (under one atmospheric of pressure) of or greater than
about 100.degree. C. The term "volatile" as used in this context
refers to all other silicone oils. Suitable organopolysiloxanes can
be selected from a wide variety of silicones spanning a broad range
of volatilities and viscosities. Examples of suitable
organopolysiloxane oils include polyalkylsiloxanes, cyclic
polyalkylsiloxanes, and polyalkylarylsiloxanes.
Polyalkylsiloxanes usefil in the composition herein include
polyalkylsiloxanes with viscosities of from about 0.5 to about
1,000,000 centistokes at 25.degree. C. Such polyalkylsiloxanes can
be represented by the general chemical formula R.sub.3 SiO[R.sub.2
SiO].sub.x SiR.sub.3 wherein R is an alkyl group having from one to
about 30 carbon atoms (preferably R is methyl or ethyl, more
preferably methyl; also mixed alkyl groups can be used in the same
molecule), and x is an integer from 0 to about 10,000, chosen to
achieve the desired molecular weight which can range to over about
10,000,000. Commercially available polyalkylsiloxanes include the
polydimethylsiloxanes, which are also known as dimethicones,
examples of which include the Vicasil.RTM. series sold by General
Electric Company and the Dow Corning.RTM. 200 series sold by Dow
Corning Corporation. Specific examples of suitable
polydimethylsiloxanes include Dow Corning.RTM. 200 fluid having a
viscosity of 0.65 centistokes and a boiling point of 100.degree.
C., Dow Corning.RTM. 225 fluid having a viscosity of 10 centistokes
and a boiling point greater than 200.degree. C., and Dow
Corning.RTM. 200 fluids having viscosities of 50, 350, and 12,500
centistokes, respectively, and boiling points greater than
200.degree. C. Suitable dimethicones include those represented by
the chemical formula (CH.sub.3).sub.3 SiO[(CH.sub.3).sub.2
SiO].sub.x [CH.sub.3 RSiO].sub.y Si(CH.sub.3).sub.3 wherein R is
straight or branched chain alkyl having from two to about 30 carbon
atoms and x and y are each integers of 1 or greater selected to
achieve the desired molecular weight which can range to over about
10,000,000. Examples of these alkyl-substituted dimethicones
include cetyl dimethicone and lauryl dimethicone.
Cyclic polyalkylsiloxanes suitable for use in the composition
include those represented by the chemical formula [SiR.sub.2
-O].sub.n wherein R is an alkyl group (preferably R is methyl or
ethyl, more preferably methyl) and n is an integer from about 3 to
about 8, more preferably n is an integer from about 3 to about 7,
and most preferably n is an integer from about 4 to about 6. When R
is methyl, these materials are typically referred to as
cyclomethicones. Commercially available cyclomethicones include Dow
Corning.RTM. 244 fluid having a viscosity of 2.5 centistokes, and a
boiling point of 172.degree. C., which primarily contains the
cyclomethicone tetramer (i.e. n=4), Dow Corning.RTM. 344 fluid
having a viscosity of 2.5 centistokes and a boiling point of
178.degree. C., which primarily contains the cyclomethicone
pentamer (i.e. n=5), Dow Corning.RTM. 245 fluid having a viscosity
of 4.2 centistokes and a boiling point of 205.degree. C., which
primarily contains a mixture of the cyclomethicone tetramer and
pentamer (i.e. n=4 and 5), and Dow Corning.RTM. 345 fluid having a
viscosity of 4.5 centistokes and a boiling point of 217.degree.,
which primarily contains a mixture of the cyclomethicone tetramer,
pentamer, and hexamer (i.e. n=4, 5, and 6).
Also useful are materials such as trimethylsiloxysilicate, which is
a polymeric material corresponding to the general chemical formula
[(CH.sub.2).sub.3 SiO.sub.1/2 ].sub.x [SiO.sub.2 ]y, wherein x is
an integer from about 1 to about 500 and y is an integer from about
1 to about 500. A commercially available trimethylsiloxysilicate is
sold as a mixture with dimethicone as Dow Corning.RTM. 593
fluid.
Dimethiconols are also suitable for use in the composition. These
compounds can be represented by the chemical formulas R.sub.3
SiO[R.sub.2 SiO].sub.x SiR.sub.2 OH and HOR.sub.2 SiO[R.sub.2
SiO].sub.x SiR.sub.2 OH wherein R is an alkyl group (preferably R
is methyl or ethyl, more preferably methyl) and x is an integer
from 0 to about 500, chosen to achieve the desired molecular
weight. Commercially available dimethiconols are typically sold as
mixtures with dimethicone or cyclomethicone (e.g. Dow Corning.RTM.
1401, 1402, and 1403 fluids).
Polyalkylaryl siloxanes are also suitable for use in the
composition. Polymethylphenyl siloxanes having viscosities from
about 15 to about 65 centistokes at 25.degree. C. are especially
useful.
Preferred for use herein are organopolysiloxanes selected from the
group consisting of polyalkylsiloxanes, alkyl substituted
dimethicones, cyclomethicones, trimethylsiloxysilicates,
dimethiconols, polyalkylaryl siloxanes, and mixtures thereof. More
preferred for use herein are polyalkylsiloxanes and
cyclomethicones. Preferred among the polyalkylsiloxanes are
dimethicones.
As stated above, the continuous silicone phase may containi one or
more non-silicone oils. Concentrations of non-silicone oils in the
continuous silicone phase are preferably minimized or avoided
altogether so as to further enhance oxidative stability of the
selected retinoid in the compositions. Suitable non-silicone oils
have a melting point of about 25.degree. C. or less under about one
atmosphere of pressure. Examples of non-silicone oils suitable for
use in the continuous silicone phase are those well known in the
chemical arts in topical personal care products in the form of
water-in-oil emulsions, e.g., mineral oil, vegetable oils,
synthetic oils, semisynthetic oils, etc.
(ii) Dispersed aqueous phase
The topical compositions of the present invention comprise from
about 30% to about 90%, more preferably from about 50% to about
85%, and most preferably from about 70% to about 80% of a dispersed
aqueous phase. In emulsion technology, the term "dispersed phase"
is a term well-known to one skilled in the art which means that the
phase exists as small particles or droplets that are suspended in
and surrounded by a continuous phase. The dispersed phase is also
known as the internal or discontinuous phase. The dispersed aqueous
phase is a dispersion of small aqueous particles or droplets
suspended in and surrounded by the continuous silicone phase
described hereinbefore.
The aqueous phase can be water, or a combination of water and one
or more water soluble or dispersible ingredients. Nonlimiting
examples of such optional ingredients include thickeners, acids,
bases, salts, chelants, gums, water-soluble or dispersible alcohols
and polyols, buffers, preservatives, sunscreening agents,
colorings, and the like.
The topical compositions of the present invention will typically
comprise from about 25% to about 90%, preferably from about 40% to
about 80%, more preferably from about 60% to about 80%, water in
the dispersed aqueous phase by weight of the composition.
(iii) Emulsifier for dispersing the aqueous phase
The water-in-silicone emulsions of the present invention preferably
comprise an emulsifier. In a preferred embodiment, the composition
contains from about 0.1% to about 10% emulsifier, more preferably
from about 0.5% to about 7.5%, most preferably from about 1% to
about 5%, emulsifier by weight of the composition. The emulsifier
helps disperse and suspend the aqueous phase within the continuous
silicone phase.
A wide variety of emulsifying agents can be employed herein to form
the preferred water-in-silicone emulsion. Known or conventional
emulsifying agents can be used in the composition, provided that
the selected emulsifying agent is chemically and physically
compatible with essential components of the composition, and
provides the desired dispersion characteristics. Suitable
emulsifiers include silicone emulsifiers, non-silicon-containing
emulsifiers, and mixtures thereof, known by those skilled in the
art for use in topical personal care products. Preferably these
emulsifiers have an HLB value of or less than about 14, more
preferably from about 2 to about 14, and most preferably from about
4 to about 14. Emulsifiers having an HLB value outside of these
ranges can be used in combination with other emulsifiers to achieve
an effective weighted average HLB for the combination that falls
within these ranges.
Silicone emulsifiers are preferred. A wide variety of silicone
emulsifiers are useful herein. These silicone emulsifiers are
typically organically modified organopolysiloxanes, also known to
those skilled in the art as silicone surfactants. Useful silicone
emulsifiers include dimethicone copolyols. These materials are
polydimethyl siloxanes which have been modified to include
polyether side chains such as polyethylene oxide chains,
polypropylene oxide chains, mixtures of these chains, and polyether
chains containing moieties derived from both ethylene oxide and
propylene oxide. Other examples include alkyl-modified dimethicone
copolyols, i.e., compounds which contain C2-C30 pendant side
chains. Still other useful dimethicone copolyols include materials
having various cationic, anionic, amphoteric, and zwitterionic
pendant moieties.
The dimethicone copolyol emulsifiers useful herein can be described
by the following general structure: ##STR4##
wherein R is C1-C30 straight, branched, or cyclic alkyl and R.sup.2
is selected from the group consisting of
and
wherein n is an integer from 3 to about 10; R.sup.3 and R.sup.4 are
selected from the group consisting of H and C1-C6 straight or
branched chain alkyl such that R.sup.3 and R.sup.4 are not
simultaneously the same; and m, o, x, and y are selected such that
the molecule has an overall molecular weight from about 200 to
about 10,000,000, with m, o, x, and y being independently selected
from integers of zero or greater such that m and o are not both
simultaneously zero, and z being independently selected from
integers of 1 or greater. It is recognized that positional isomers
of these copolyols can be achieved. The chemical representations
depicted above for the R.sup.2 moieties containing the R.sup.3 and
R.sup.4 groups are not meant to be limiting but are shown as such
for convenience.
Also useful herein, although not strictly classified as dimethicone
copolyols, are silicone surfactants as depicted in the structures
in the previous paragraph wherein R.sup.2 is:
wherein R.sup.5 is a cationic, anionic, amphoteric, or zwitterionic
moiety.
Nonlimiting examples of dimethicone copolyols and other silicone
surfactants useful as emulsifiers herein include
polydimethylsiloxane polyether copolymers with pendant polyethylene
oxide sidechains, polydimethylsiloxane polyether copolymers with
pendant polypropylene oxide sidechains, polydimethylsiloxane
polyether copolymers with pendant mixed polyethylene oxide and
polypropylene oxide sidechains, polydimethylsiloxane polyether
copolymers with pendant mixed poly(ethylene)(propylene)oxide
sidechains, polydimethylsiloxane polyether copolymers with pendant
organobetaine sidechains, polydimethylsiloxane polyether copolymers
with pendant carboxylate sidechains, polydimethylsiloxane polyether
copolymers with pendant quaternary ammonium sidechains; and also
further modifications of the preceding copolymers containing
pendant C2-C30 straight, branched, or cyclic alkyl moieties.
Examples of commercially available dimethicone copolyols useful
herein sold by Dow Corning Corporation are Dow Corning.RTM. 190,
193, Q2-5220, 2501 Wax, 2-5324 fluid, and 3225C (this later
material being sold as a mixture with cyclomethicone). Cetyl
dimethicone copolyol is commercially available as a mixture with
polyglyceryl-4 isostearate (and) hexyl laurate and is sold under
the tradename ABIL.RTM. WE-09 (available from Goldschmidt). Cetyl
dimethicone copolyol is also commercially available as a mixture
with hexyl laurate (and) polyglyceryl-3 oleate (and) cetyl
dimethicone and is sold under the tradename ABIL.RTM. WS-08 (also
available from Goldschmidt). Other nonlimiting examples of
dimethicone copolyols also include lauryl dimethicone copolyol,
dimethicone copolyol acetate, diemthicone copolyol adipate,
dimethicone copolyolamine, dimethicone copolyol behenate,
dimethicone copolyol butyl ether, dimethicone copolyol hydroxy
stearate, dimethicone copolyol isostearate, dimethicone copolyol
laurate, dimethicone copolyol methyl ether, dimethicone copolyol
phosphate, and dimethicone copolyol stearate. See International
Cosmetic Ingredient Dictionary, Fifth Edition, 1993, which is
incorporated by reference herein in its entirety.
Dimethicone copolyol emulsifiers useful herein are described, for
example, in U.S. Pat. No. 4,960,764, to Figueroa, Jr. et al.,
issued Oct. 2, 1990; European Patent No. EP 330,369, to SanoGueira,
published Aug. 30, 1989; G. H. Dahms, et al., "New Formulation
Possibilities Offered by Silicone Copolyols," Cosmetics &
Toiletries, vol. 110, pp. 91-100, March 1995; M. E. Carlotti et
al., "Optimization of W/O-S Emulsions And Study Of The Quantitative
Relationships Between Ester Structure And Emulsion Properties," J.
Dispersion Science And Technology, 13(3), 315-336 (1992); P.
Hameyer, "Comparative Technological Investigations of Organic and
Organosilicone Emulsifiers in Cosmetic Water-in-Oil Emulsion
Preparations," HAPPI 28(4), pp. 88-128 (1991); J. Smid-Korbar et
al., "Efficiency and usability of silicone surfactants in
emulsions," Provisional Communication, International Journal of
Cosmetic Science, 12, 135-139 (1990); and D. G. Krzysik et al., "A
New Silicone Emulsifier For Water-in-Oil Systems," Drug and
Cosmetic Industly, vol. 146(4) pp. 28-81 (April 1990); incorporated
by reference herein in their entirety.
Among the non-silicon-containing emulsifiers useful herein are
various non-ionic and anionic emulsifying agents such as sugar
esters and polyesters, alkoxylated sugar esters and polyesters,
C1-C30 fatty acid esters of C1-C30 fatty alcohols, alkoxylated
derivatives of C1-C30 fatty acid esters of C1-C30 fatty alcohols,
alkoxylated ethers of C1-C30 fatty alcohols, polyglyceryl esters of
C1-C30 fatty acids, C1-C30 esters of polyols, C1-C30 ethers of
polyols, alkyl phosphates, polyoxyalkylene fatty ether phosphates,
fatty acid amides, acyl lactylates, soaps, and mixtures thereof.
Other suitable emulsifiers are described, for example, in
McCutcheon's, Detergents and Emulsifiers, North American Edition
(1986), published by Allured Publishing Corporation; U.S. Pat. No.
5,011,681 to Ciotti et al., issued Apr. 30, 1991; U.S. Pat. No.
4,421,769 to Dixon et al., issued Dec. 20, 1983; and U.S. Pat. No.
3,755,560 to Dickert et al., issued Aug. 28, 1973; these references
are incorporated herein by reference in their entirety.
Nonlimiting examples of these non-silicon-containing emulsifiers
include: polyethylene glycol 20 sorbitan monolaurate (Polysorbate
20), polyethylene glycol 5 soya sterol, Steareth-20, Ceteareth-20,
PPG-2 methyl glucose ether distearate, Ceteth-10, Polysorbate 80,
cetyl phosphate, potassium cetyl phosphate, diethanolamine cetyl
phosphate, Polysorbate 60, glyceryl stearate, PEG-100 stearate,
polyoxyethylene 20 sorbitan trioleate (Polysorbate 85), sorbitan
monolaurate, polyoxyethylene 4 lauryl ether sodium stearate,
polyglyceryl-4 isostearate, hexyl laurate, steareth-20,
ceteareth-20, PPG-2 methyl glucose ether distearate, ceteth-10,
diethanolamine cetyl phosphate, glyceryl stearate, PEG-100
stearate, and mixtures thereof.
b) Oil-in-Water Emulsions
Other preferred topical carriers include oil-in-water emulsions,
having a continuous aqueous phase and a hydrophobic,
water-insoluble phase ("oil phase") dispersed therein. An
especially preferred oil-in-water emulsion, containing a
structuring agent, hydrophilic surfactant and water, is described
in detail hereinafter.
(i) Structuring Agent
A preferred oil-in-water emulsion comprises a structuring agent to
assist in the formation of a liquid crystalline gel network
structure. Concentrations of such structuring agents are from about
1% to about 20%, preferably from about 1% to about 10%, more
preferably from about 3% to about 9% by weight of the topical
carrier.
Suitable structuring agents are those selected from the group
consisting of saturated C.sub.16 to C.sub.30 fatty alcohols,
saturated C.sub.16 to C.sub.30 fatty alcohols containing from about
1 to about 5 moles of ethylene oxide, saturated C.sub.16 to
C.sub.30 diols, saturated C.sub.16 to C.sub.30 monoglycerol ethers,
saturated C.sub.16 to C.sub.30 hydroxy fatty acids, and mixtures
thereof, having a melting point of at least about 45.degree. C.
Preferred structuring agents include stearyl alcohol, cetyl
alcohol, behenyl alcohol, stearic acid, palmitic acid, the
polyethylene glycol ether of stearyl alcohol having an average of
about 1 to about 5 ethylene oxide units, the polyethylene glycol
ether of cetyl alcohol having an average of about 1 to about 5
ethylene oxide units, and mixtures thereof. More preferred
structuring agents of the present invention are selected from the
group consisting of stearyl alcohol, cetyl alcohol, behenyl
alcohol, the polyethylene glycol ether of stearyl alcohol having an
average of about 2 ethylene oxide units (steareth-2), the
polyethylene glycol ether of cetyl alcohol having an average of
about 2 ethylene oxide units, and mixtures thereof. Even more
preferred structuring agents are selected from the group consisting
of stearyl alcohol, cetyl alcohol, behenyl alcohol, steareth-2, and
mixtures thereof. Most preferred is steareth-2, available under the
tradename of Brij.RTM. 72 from ICI Americas.
(ii) Hydrophilic Surfactant
The preferred oil-in-water emulsions comprise from about 0.05% to
about 10%, preferably from about 1% to about 6%, and more
preferably from about 1% to about 3% of at least one hydrophilic
surfactant which can disperse the hydrophobic materials in the
water phase (percentages by weight of the topical carrier). The
surfactant, at a minimum, must be hydrophilic enough to disperse in
water.
Suitable surfactants include any of a wide variety of known
cationic, anionic, zwitterionic, and amphoteric surfactants. See
McCutcheon's, Detergents and Emulsifiers, North American Edition
(1986), published by Allured Publishing Corporation; U.S. Pat. No.
5,011,681; U.S. Pat. No. 4,421,769; and U.S. Pat. No. 3,755,560;
these references are incorporated herein by reference in their
entirety.
The exact surfactant chosen will depend upon the pH of the
composition and the other components present.
Preferred are cationic surfactants, especially dialkyl quaternary
ammonium compounds, examples of which are described in U.S. Pat.
No. 5,151,209; U.S. Pat. No. 5,151,210; U.S. Pat. No. 5,120,532;
U.S. Pat. No. 4,387,090; U.S. Pat. No. 3,155,591; U.S. Pat. No.
3,929,678; U.S. Pat. No. 3,959,461; McCutcheon's. Detergents &
Emulsifiers, (North American edition 1979) M.C. Publishing Co.; and
Schwartz, et al., Surface Active Agents, Their Chemistry and
Technology, New York: Interscience Publishers, 1949; which
descriptions are incorporated herein by reference. The cationic
surfactants useful herein include cationic ammonium salts such as
those having the formula: ##STR5##
wherein R.sub.1, is an alkyl group having from about 12 to about 30
carbon atoms, or an aromatic, aryl or alkaryl group having from
about 12 to about 30 carbon atoms; R.sub.2, R.sub.3, and R.sub.4
are independently selected from hydrogen, an alkyl group having
from about 1 to about 22 carbon atoms, or aromatic, aryl or alkaryl
groups having from about 12 to about 22 carbon atoms; and X is any
compatible anion, preferably selected from the group consisting of
chloride, bromide, iodide, acetate, phosphate, nitrate, sulfate,
methyl sulfate, ethyl sulfate, tosylate, lactate, citrate,
glycolate, and mixtures thereof. Additionally, the alkyl groups of
R.sub.1, R.sub.2, R.sub.3, and R.sub.4 can also contain ester
and/or ether linkages, or hydroxy or amino group substituents
(e.g., the alkyl groups can contain polyethylene glycol and
polypropylene glycol moieties).
More preferably, R.sub.1 is an alkyl group having from about 12 to
about 22 carbon atoms; R.sub.2 is selected from H or an alkyl group
having from about 1 to about 22 carbon atoms; R.sub.3 and R.sub.4
are independently selected from H or an alkyl group having from
about 1 to about 3 carbon atoms; and X is as described
previously.
Most preferably, R.sub.1 is an alkyl group having from about 12 to
about 22 carbon atoms; R.sub.2, R.sub.3, and R.sub.4 are selected
from H or an alkyl group having from about 1 to about 3 carbon
atoms; and X is as described previously.
Alternatively, other useful cationic emulsifiers include
amino-amides, wherein in the above structure R.sub.1 is
alternatively R.sub.5 CONH--(CH.sub.2).sub.n, wherein R.sub.5 is an
alkyl group having from about 12 to about 22 carbon atoms, and n is
an integer from about 2 to about 6, more preferably from about 2 to
about 4, and most preferably from about 2 to about 3. Nonlimiting
examples of these cationic emulsifiers include stearamidopropyl
PG-dimonium chloride phosphate, behenamidopropyl PG dimonium
chloride, stearamidopropyl ethyldimonium ethosulfate,
stearamidopropyl dimethyl (myristyl acetate) ammonium chloride,
stearamidopropyl dimethyl cetearyl ammonium tosylate,
stearamidopropyl dimethyl ammonium chloride, stearamidopropyl
dimethyl ammonium lactate, and mixtures thereof. Especially
preferred is behenamidopropyl PG dimonium chloride.
Nonlimiting examples of quaternary ammonium salt cationic
surfactants include those selected from the group consisting of
cetyl ammonium chloride, cetyl ammonium bromide, lauryl ammonium
chloride, lauryl ammonium bromide, stearyl ammonium chloride,
stearyl ammonium bromide, cetyl dimethyl ammonium chloride, cetyl
dimethyl ammonium bromide, lauryl dimethyl ammonium chloride,
lauryl dimethyl ammonium bromide, stearyl dimethyl ammonium
chloride, stearyl dimethyl ammonium bromide, cetyl trimethyl
ammonium chloride, cetyl trimethyl ammonium bromide, lauryl
trimethyl ammonium chloride, lauryl trimethyl ammonium bromide,
stearyl trimethyl ammonium chloride, stearyl trimethyl ammonium
bromide, lauryl dimethyl ammonium chloride, stearyl dimethyl cetyl
ditallow dimethyl ammonium chloride, dicetyl ammonium chloride,
dicetyl ammonium bromide, dilauryl ammonium chloride, dilauryl
ammonium bromide, distearyl ammonium chloride, distearyl ammonium
bromide, dicetyl methyl ammonium chloride, dicetyl methyl ammonium
bromide, dilauryl methyl ammonium chloride, dilauryl methyl
ammonium bromide, distearyl methyl ammonium chloride, distearyl
methyl ammonium bromide, and mixtures thereof. Additional
quaternary ammonium salts include those wherein the C.sub.12 to
C.sub.30 alkyl carbon chain is derived from a tallow fatty acid or
from a coconut fatty acid. The term "tallow" refers to an alkyl
group derived from tallow fatty acids (usually hydrogenated tallow
fatty acids), which generally have mixtures of alkyl chains in the
C.sub.16 to C.sub.18 range. The term "coconut" refers to an alkyl
group derived from a coconut fatty acid, which generally have
mixtures of alkyl chains in the C.sub.12 to C.sub.14 range.
Examples of quaternary ammonium salts derived from these tallow and
coconut sources include ditallow dimethyl ammonium chloride,
ditallow dimethyl ammonium methyl sulfate, di(hydrogenated tallow)
dimethyl ammonium chloride, di(hydrogenated tallow) dimethyl
ammonium acetate, ditallow dipropyl ammonium phosphate, ditallow
dimethyl ammonium nitrate, di(coconutalkyl)dimethyl ammonium
chloride, di(coconutalkyl)dimethyl ammonium bromide, tallow
ammonium chloride, coconut ammonium chloride, stearamidopropyl
PG-dimonium chloride phosphate, steararnidopropyl ethyldimonium
ethosulfate, stearamidopropyl dimethyl (myristyl acetate) ammonium
chloride, stearamidopropyl dimethyl cetearyl ammonium tosylate,
stearamidopropyl dimethyl ammonium chloride, stearamidopropyl
dimethyl ammonium lactate, and mixtures thereof. An example of a
quaternary ammonium compound having an alkyl group with an ester
linkage is ditallowyl oxyethyl dimethyl ammonium chloride.
More preferred cationic surfactants are those selected from the
group consisting of behenamidopropyl PG dimonium chloride, dilauryl
dimethyl ammonium chloride, distearyl dimethyl ammonium chloride,
dimyristyl dimethyl ammonium chloride, dipalmityl dimethyl ammonium
chloride, distearyl dimethyl ammonium chloride, stearamidopropyl
PG-dimonium chloride phosphate, stearamidopropyl ethyldiammonium
ethosulfate, stearamidopropyl dimethyl (myristyl acetate) ammonium
chloride, stearamidopropyl dimethyl cetearyl ammonium tosylate,
stearamidopropyl dimethyl ammonium chloride, stearamidopropyl
dimethyl ammonium lactate, and mixtures thereof.
Most preferred cationic surfactants are those selected from the
group consisting of behenamidopropyl PG dimonium chloride, dilauryl
dimethyl ammonium chloride, distearyl dimethyl ammonium chloride,
dimyristyl dimethyl ammonium chloride, dipalmityl dimethyl ammonium
chloride, and mixtures thereof.
A preferred combination of cationic surfactant and structuring
agent is behenamidopropyl PG dimonium chloride and/or behenyl
alcohol, wherein the ratio is preferably optimized to maintained to
enhance physical and chemical stability, especially when such a
combination contains ionic and/or highly polar solvents. This
combination is especially useful for delivery of sunscreening
agents such as zinc oxide and octyl methoxycinnamate.
A wide variety of anionic surfactants are also useful herein. See,
e.g., U.S. Pat. No. 3,929,678, to Laughlin et al., issued Dec. 30,
1975, which is incorporated herein by reference in its entirety.
Nonlimiting examples of anionic surfactants include the alkoyl
isethionates, and the alkyl and alkyl ether sulfates. The alkoyl
isethionates typically have the formula RCO--OCH.sub.2 CH.sub.2
SO.sub.3 M wherein R is alkyl or alkenyl of from about 10 to about
30 carbon atoms, and M is a water-soluble cation such as ammonium,
sodium, potassium and triethanolamine. Nonlimiting examples of
these isethionates include those alkoyl isethionates selected from
the group consisting of ammonium cocoyl isethionate, sodium cocoyl
isethionate, sodium lauroyl isethionate, sodium stearoyl
isethionate, and mixtures thereof.
The alkyl and alkyl ether sulfates typically have the respective
formulae ROSO.sub.3 M and RO(C.sub.2 H.sub.4 O).sub.x SO.sub.3 M,
wherein R is alkyl or alkenyl of from about 10 to about 30 carbon
atoms, x is from about 1 to about 10, and M is a water-soluble
cation such as ammonium, sodium, potassium and triethanolamine.
Another suitable class of anionic surfactants are the water-soluble
salts of the organic, sulfuric acid reaction products of the
general formula:
wherein R.sub.1 is chosen from the group consisting of a straight
or branched chain, saturated aliphatic hydrocarbon radical having
from about 8 to about 24, preferably about 10 to about 16, carbon
atoms; and M is a cation. Still other anionic synthetic surfactants
include the class designated as succinamates, olefin sulfonates
having about 12 to about 24 carbon atoms, and .beta.-alkyloxy
alkane sulforiates. Examples of these materials are sodium lauryl
sulfate and ammonium lauryl sulfate.
Other anionic materials useful herein are soaps (i.e. alkali metal
salts, e.g., sodium or potassium salts) of fatty acids, typically
having from about 8 to about 24 carbon atoms, preferably from about
10 to about 20 carbon atoms. The fatty acids used in making the
soaps can be obtained from natural sources such as, for instance,
plant or animal-derived glycerides (e.g., palm oil, coconut oil,
soybean oil, castor oil, tallow, lard, etc.) The fatty acids can
also be synthetically prepared. Soaps are described in more detail
in U.S. Pat. No. 4,557,853, cited above.
Amphoteric and zwitterionic surfactants are also useful herein.
Examples of amphoteric and zwitterionic surfactants which can be
used in the compositions of the present invention are those which
are broadly described as derivatives of aliphatic secondary and
tertiary amines in which the aliphatic radical can be straight or
branched chain and wherein one of the aliphatic substituents
contains from about 8 to about 22 carbon atoms (preferably C.sub.8
-C.sub.18) and one contains an anionic water solubilizing group,
e.g., carboxy, sulfonate, sulfate, phosphate, or phosphonate.
Examples are alkyl imino acetates, and iminodialkanoates and
aminoalkanoates of the formulas RN[CH.sub.2).sub.m CO.sub.2
M].sub.2 and RNH(CH.sub.2).sub.m CO.sub.2 M wherein m is from 1 to
4, R is a C.sub.8 -C.sub.22 alkyl or alkenyl, and M is H, alkali
metal, alkaline earth metal ammonium, or alkanolammonium. Also
included are imidazolinium and ammonium derivatives. Specific
examples of suitable amphoteric surfactants include sodium
3-dodecyl-aminopropionate, sodium 3-dodecylaminopropane sulfonate,
N-alkyltaurines such as the one prepared by reacting dodecylamine
with sodium isethionate according to the teaching of U.S. Pat. No.
2,658,072 which is incorporated herein by reference in its
entirety; N-higher alkyl aspartic acids such as those produced
according to the teaching of U.S. Pat. No. 2,438,091 which is
incorporated herein by reference in its entirety; and the products
sold under the trade name "Miranol" and described in U.S. Pat. No.
2,528,378, which is incorporated herein by reference in its
entirety. Other examples of useful amphoterics include phosphates,
such as coamidopropyl PG-dimonium chloride phosphate (commercially
available as Monaquat PTC, from Mona Corp.).
Also useful herein as amphoteric or zwitterionic surfactants are
the betaines. Examples of betaines include the higher alkyl
betaines, such as coco dimethyl carboxymethyl betaine, lauryl
dimethyl carboxymethyl betaine, lauryl dimethyl alphacarboxyethyl
betaine, cetyl dimethyl carboxymethyl betaine, cetyl dimethyl
betaine (available as Lonzaine 16SP from Lonza Corp.), lauryl
blis-(2-hydroxyethyl) carboxymethyl betaine, stearyl
bis-(2-hydroxypropyl) carboxymethyl betaine, oleyl dimethyl
gamma-carboxypropyl betaine, lauryl
bis-(2-hydroxypropyl)alpha-carboxyethyl betaine, coco dimethyl
sulfopropyl betaine, stearyl dimethyl sulfopropyl betaine, lauryl
dimethyl sulfoethyl betaine, lauryl bis-(2-hydroxyethyl)
sulfopropyl betaine, and amidobetaines and amidosulfobetaines
(wherein the RCONH(CH.sub.2).sub.3 radical is attached to the
nitrogen atom of the betaine), oleyl betaine (available as
amphoteric Velvetex OLB-50 from Henkel), and cocamidopropyl betaine
(available as Velvetex BK-35 and BA-35 from Henkel).
Other useful amphoteric and zwitterionic surfactants include the
sultaines and hydroxysultaines such as cocamidopropyl
hydroxysultaine (available as Mirataine CBS from Rhone-Poulenc),
and the alkanoyl sarcosinates corresponding to the formula
RCON(CH.sub.3)CH.sub.2 CH.sub.2 CO.sub.2 M wherein R is alkyl or
alkenyl of about 10 to about 20 carbon atoms, and M is a
water-soluble cation such as ammonium, sodium, potassium and
trialkanolamine (e.g., triethanolamine), a preferred example of
which is sodium lauroyl sarcosinate.
(iii) Water
The preferred oil-in-water emulsion comprises from about 25% to
about 98%, preferably from about 65% to about 95%, more preferably
from about 70% to about 90% water by weight of the topical
carrier.
The hydrophobic phase is dispersed in the continuous aqueous phase.
The hydrophobic phase may contain water insoluble or partially
soluble materials such as are known in the art, including but not
limited to the silicones described herein in reference to
silicone-in-water emulsions, and other oils and lipids such as
described above in reference to emulsions.
The topical compositions of the subject invention, including but
not limited to lotions and creams, may comprise a dermatologically
acceptable emollient. Such compositions preferably contain from
about 2% to about 50% of the emollient. As used herein, "emollient"
refers to a material useful for the prevention or relief of
dryness, as well as for the protection of the skin. A wide variety
of suitable emollients are known and may be used herein. Sagarin,
Cosmetics, Science and Technology, 2nd Edition, Vol. 1, pp. 32-43
(1972), incorporated herein by reference, contains numerous
examples of materials suitable as an emollient. A preferred
emollient is glycerin. Glycerin is preferably used in an amount of
from or about 0.001 to or about 20%, more preferably from or about
0.01 to or about 10%, most preferably from or about 0.1 to or about
5%, e.g., 3%.
Lotions and creams according to the present invention generally
comprise a solution carrier system and one or more emollients.
Lotions typically comprise from about 1% to about 20%, preferably
from about 5% to about 10%, of emollient; from about 50% to about
90%, preferably from about 60% to about 80%, water; and the vitamin
B.sub.3 compound in the above described amounts. A cream typically
comprises from about 5% to about 50%, preferably from about 10% to
about 20%, of emollient; from about 45% to about 85%, preferably
from about 50% to about 75%, water; and the vitamin B.sub.3
compound in the above described amounts.
Ointments of the present invention may comprise a simple carrier
base of animal or vegetable oils or semi-solid hydrocarbons
(oleaginous); absorption ointment bases which absorb water to form
emulsions; or water soluble carriers, e.g., a water soluble
solution carrier. Ointments may further comprise a thickening
agent, such as described in Sagarin, Cosmetics, Science and
Technology, 2nd Edition, Vol. 1, pp. 72-73 (1972), incorporated
herein by reference, and/or an emollient. For example, an ointment
may comprise from about 2% to about 10% of an emollient; from about
0.1% to about 2% of a thickening agent; and the vitamin B.sub.3
compound in the above described amount.
Compositions of this invention useful for cleansing ("cleansers")
are formulated with a suitable carrier, e.g., as described above,
and preferably contain, in addition to the vitamin B.sub.3 compound
in the above described amounts, from about 1% to about 90%, more
preferably from about 5% to about 10%, of a dermatologically
acceptable surfactant. The surfactant is suitably selected from
anionic, nonionic, zwitterionic, amphoteric and ampholytic
surfactants, as well as mixtures of these surfactants. Such
surfactants are well known to those skilled in the detergency art.
Nonlimiting examples of possible surfactants include isoceteth-20,
sodium methyl cocoyl taurate, sodium methyl oleoyl taurate, and
sodium lauryl sulfate. See U.S. Pat. No. 4,800,197, to Kowcz et
al., issued Jan. 24, 1989, which is incorporated herein by
reference in its entirety, for exemplary surfactants useful herein.
Examples of a broad variety of additional surfactants useful herein
are described in McCutcheon's Detergents and Emulsifiers, North
American Edition (1986), published by Allured Publishing
Corporation, which is incorporated herein by reference in its
entirety. The cleansing compositions can optionally contain, at
their art-established levels, other materials which are
conventionally used in cleansing compositions.
The physical form of the cleansing compositions is not critical.
The compositions can be, for example, formulated as toilet bars,
liquids, shampoos, bath gels, hair conditioners, hair tonics,
pastes, or mousses. Toilet bars are most preferred since this is
the form of cleansing agent most commonly used to wash the skin.
Rinse-off cleansing compositions, such as shampoos, require a
delivery system adequate to deposit sufficient levels of actives on
the skin and scalp. A preferred delivery system involves the use of
insoluble complexes. For a more complete disclosure of such
delivery sytems, see U.S. Pat. No. 4,835,148, Barford et al.,
issued May 30, 1989, incorporated herein by reference in its
entirety.
As used herein, the term "foundation" refers to a liquid,
semi-liquid, semi-solid, or solid skin cosmetic which includes, but
is not limited to lotions, creams, gels, pastes, cakes, and the
like. Typically the foundation is used over a large area of the
skin, such as over the face, to provide a particular look.
Foundations are typically used to provide an adherent base for
color cosmetics such as rouge, blusher, powder and the like, and
tend to hide skin imperfections and impart a smooth, even
appearance to the skin. Foundations of the present invention
include a dermatologically acceptable carrier for the vitamin
B.sub.3 compound and may include conventional ingredients such as
oils, colorants, pigments, emollients, fragrances, waxes,
stabilizers, and the like. Exemplary carriers and such other
ingredients which are suitable for use herein are described, for
example, in copending patent application Ser. No. 08/430,961, filed
on Apr. 28, 1995 in the names of Marcia L. Canter, Brain D.
Barford, and Brian D. Hofrichter, incorporated herein by
reference.
The compositions of the present invention are preferably formulated
to have a pH of 10.5 or below. The pH values of these compositions
preferably range from about 2 to about 10.5, more preferably from
about 3 to about 8, even more preferably from about 4 to about 7,
and also from about 4.5 to about 5.5.
Optional Components
The topical compositions of the present invention may comprise a
wide variety of optional components, provided that such optional
components are physically and chemically compatible with the
essential components described herein, and do not unduly impair
stability, efficacy or other use benefits associated with the
compositions of the present invention. Any optional ingredients
should be compatible with the vitamin B.sub.3 compound such that
its activity does not decrease unacceptably, preferably not to any
significant extent, over a useful period (preferably at least about
two years under normal storage conditions). For example, strong
oxidizing agents may be incompatible with the vitamin B.sub.3
compound such that such agents are preferably avoided. Optional
components may be dispersed, dissolved or the like in the carrier
of the present compositions.
Optional components include aesthetic agents and other active
agents. For example, the compositions may include absorbents,
abrasives, anticaking agents, antifoaming agents, antimicrobial
agents, binders, biological additives, buffering agents, bulking
agents, chemical additives, cosmetic biocides, denaturants,
cosmetic astringents, drug astringents, external analgesics, film
foirmers, humectants, opacifying agents, fragrances, pigments,
colorings, essential oils, skin sensates, emollients, skin soothing
agents, skin healing agents, pH adjusters, plasticizers,
preservatives, preservative enhancers, propellants, reducing
agents, additional skin-conditioning agents, skin penetration
enhancing agents, skin protectants, solvents, suspending agents,
emulsifiers, thickening agents, solubilizing agents, sunscreens,
sunblocks, ultraviolet light absorbers or scattering agents,
sunless tanning agents, antioxidants and/or radical scavengers,
chelating agents, sequestrants, anti-acne agents, anti-inflammatory
agents, anti-androgens, depilation agents, desquamation
agents/exfoliants, organic hydroxy acids, vitamins and derivatives
thereof, and natural extracts. Such other materials are known in
the art. Nonexclusive examples of such materials are described in
Harry's Cosmeticology, 7th Ed., Harry & Wilkinson (Hill
Publishers, London 1982); in Pharmaceutical Dosage Forms--Disperse
Systems; Lieberman, Rieger & Banker, Vols. 1 (1988) & 2
(1989); Marcel Decker, Inc.; in The Chemistry and Manufacture of
Cosmetics, 2nd. Ed., deNavarre (Van Nostrand 1962-1965); and in The
Handbook of Cosmetic Science and Technology, 1st Ed. Knowlton &
Pearce (Elsevier 1993).
It has been found that certain compounds may negatively impact the
skin appearance benefits otherwise provided by the vitamin B.sub.3
compound. Such compounds include ascorbic acid and N-acetyl
cysteine. Without intending to be bound or limited by theory, it is
believed that these compounds may form large complexes, e.g.,
salts, with the vitamin B.sub.3 compound which reduce the
availability of the vitamin B.sub.3 compound to the skin. Such
complexes are believed to have a relatively high molecular weight
which decreases their availability to the skin. Therefore, in one
embodiment of the invention, the compositions do not contain these
compounds or compounds which are capable of forming similarly large
complexes with the vitamin B.sub.3 compound. In another embodiment,
where the composition contains these compounds or compounds which
are capable of forming large complexes with the vitamin B.sub.3
compound, one or more of the approaches previously described herein
for minimizing or preventing the formation of undesirable complexes
are preferred.
For example, the impact of such compounds on the efficacy of the
vitamin B.sub.3 compound decreases with a decrease in pH such that
pH adjustments can be employed to minimize or obviate such effects.
For example, when the composition contains N-acetyl-L-cysteine, the
pH of the composition is preferably adjusted to from about 2 to
about 5, more preferably from about 3 to about 4. The adjustment of
pH to obviate substantial impacts on efficacy is well within thie
level of ordinary skill in the art.
Specific examples of optional components include the following. The
active ingredients useful herein are categorized by their cosmetic
and/or therapeutic benefit or their postulated mode of action.
However, it is to be understood that the active ingredients useful
herein can in some instances provide more than one cosmetic and/or
therapeutic benefit or operate via more than one mode of action.
Therefore, classifications herein are made for the sake of
convenience and are not intended to limit the active ingredient to
that particular application or applications listed.
A. Anti-Inflammatory Agents
A safe and effective amount of an anti-inflammatory agent may be
added to the compositions of the subject invention, preferably from
about 0.1% to about 10%, more preferably from about 0.5% to about
5%, of the composition. The anti-inflammatory agent enhances the
skin appearance benefits of the present invention, e.g., such
agents contribute to a more uniform and acceptable skin tone or
color. The exact amount of anti-inflammatory agent to be used in
the compositions will depend on the particular anti-inflammatory
agent utilized since such agents vary widely in potency.
Steroidal anti-inflammatory agents, including but not limited to,
corticosteroids such as hydrocortisone, hydroxyltriamcinolone,
alpha-methyl dexamethasone, dexamethasone-phosphate, beclomethasone
dipropionates, clobetasol valerate, desonide, desoxymethasone,
desoxycorticosterone acetate, dexamethasone, dichlorisone,
diflorasone diacetate, diflucortolone valerate, fluadrenolone,
fluclorolone acetonide, fludrocortisone, flumethasone pivalate,
fluosinolone acetonide, fluocinonide, flucortine butylesters,
fluocortolone, fluprednidene (fluprednylidene) acetate,
flurandrenolone, halcinonide, hydrocortisone acetate,
hydrocortisone butyrate, methylprednisolone, triamcinolone
acetonide, cortisone, cortodoxone, flucetonide, fludrocortisone,
difluorosone diacetate, fluradrenolone, fludrocortisone,
diflurosone diacetate, fluradrenolone acetonide, medrysone,
amcinafel, amcinafide, betamethasone and the balance of its esters,
chloroprednisone, chlorprednisone acetate, clocortelone,
clescinolone, dichlorisone, diflurprednate, flucloronide,
flunisolide, fluoromethalone, fluperolone, fluprednisolone,
hydrocortisone valerate, hydrocortisone cyclopentylpropionate,
hydrocortamate, meprednisone, paramethasone, prednisolone,
prednisone, beclomethasone dipropionate, triamcinolone, and
mixtures thereof may be used. The preferred steroidal
anti-inflammatory for use is hydrocortisone.
A second class of anti-inflammatory agents which is useful in the
compositions includes the nonsteroidal anti-inflammatory agents.
The variety of compounds encompassed by this group are well-known
to those skilled in the art. For detailed disclosure of the
chemical structure, synthesis, side effects, etc. of non-steroidal
anti-inflammatory agents, reference may be had to standard texts,
including Anti-inflammatory and Anti-Rheumatic Drugs, K. D.
Rainsford, Vol. I-III, CRC Press, Boca Raton, (1985), and
Anti-inflammatory Agents, Chemistry and Pharmacology, 1, R. A.
Scherrer, et al., Academic Press, New York (1974), each
incorporated herein by reference.
Specific non-steroidal anti-inflammatory agents useful in the
composition invention include, but are not limited to:
1) the oxicams, such as piroxicam, isoxicam, tenoxicam, sudoxicam,
and CP-14,304;
2) the salicylates, such as aspirin, disalcid, benorylate,
trilisate, safapryn, solprin, diflunisal, and fendosal;
3) the acetic acid derivatives, such as diclofenac, fenclofenac,
indomethacin, sulindac, tolmetin, isoxepac, furofenac, tiopinac,
zidometacin, acematacin, fentiazac, zomepirac, clindanac, oxepinac,
felbinac, and ketorolac;
4) the fenamates, such as mefenamic, meclofenamic, flufenamic,
niflumic, and tolfenamic acids;
5) the propionic acid derivatives, such as ibuprofen, naproxen,
benoxaprofen, flurbiprofen, ketoprofen, fenoprofen, fenbufen,
indopropfen, pirprofen, carprofen, oxaprozin, pranoprofen,
miroprofen, tioxaprofen, suprofen, alminoprofen, and tiaprofenic;
and
6) the pyrazoles, such as phenylbutazone, oxyphenbutazone,
feprazone, azapropazone, and trimethazone.
Mixtures of these non-steroidal anti-inflammatory agents may also
be employed, as well as the dermatologically acceptable salts and
esters of these agents. For example, etofenamate, a flufenamic acid
derivative, is particularly useful for topical application. Of the
nonsteroidal anti-inflammatory agents, ibuprofen, naproxen,
flufenamic acid, etofenamate, aspirin, mefenamic acid, meclofenamic
acid, piroxicam and felbinac are preferred; ibuprofen, naproxen,
etofenamate, aspirin and flufenamic acid are most preferred.
Finally, so-called "natural" anti-inflammatory agents are useful in
methods of the subject invention. Such agents may suitably be
obtained as an extract by suitable physical and/or chemical
isolation from natural sources (e.g., plants, fungi, by-products of
microorganisms). For example, candelilla wax, alpha bisabolol, aloe
vera, Manjistha (extracted from plants in the genus Rubia,
particularly Rubia Cordifolia), and Guggal (extracted from plants
in the genus Commiphora, particularly Commiphora Mukul), kola
extract, chamomile, and sea whip extract, may be used.
Additional anti-inflammatory agents useful herein include compounds
of the Licorice (the plant genus/species Glycyrrhiza glabra)
family, including glycyrrhetic acid, glycyrrhizic acid, and
derivatives thereof (e.g., salts and esters). Suitable salts of the
foregoing compounds include metal and ammonium salts. Suitable
esters include C.sub.2 -C.sub.24 saturated or unsaturated esters of
the acids, preferably C.sub.10 -C.sub.24, more preferably C.sub.16
-C.sub.24. Specific examples of the foregoing include oil soluble
licorice extract, the glycyrrhizic and glycyrrhetic acids
themselves, monoammonium glycyrrhizinate, monopotassium
glycyrrhizinate, dipotassium glycyrrhizinate, 1-beta-glycyrrhetic
acid, stearyl glycyrrhetinate, and 3-stearyloxy-glycyrrhetinic
acid, and disodium 3-succinyloxy-beta-glycyrrhetinate. Stearyl
glycyrrhetinate is preferred.
B. Retinoids
In a preferred embodiment, the compositions of the present
invention also contain a retinoid. The vitamin B.sub.3 compound and
retinoid provide unexpected benefits in regulating skin condition,
especially in therapeutically regulating signs of skin aging, more
especially wrinkles, lines, and pores. Without intending to be
bound or otherwise limited by theory, it is believed that the
vitamin B.sub.3 compound increases the conversion of certain
retinoids to trans-retinoic acid, which is believed to be the
biologically active form of the retinoid, to provide synergistic
regulation of skin condition (namely, increased conversion for
retinol, retinol esters, and retinal). In addition, the vitamin
B.sub.3 compound unexpectedly mitigates redness, inflammation,
dermatitis and the like which may otherwise be associated with
topical application of retinoid (often referred to, and hereinafter
alternatively referred to as "retinoid dermatitis"). Furthermore,
the combined vitamin B.sub.3 compound and retinoid tend to increase
the amount and activity of thioredoxin, which tends to increase
collagen expression levels via the protein AP-1. Therefore, the
present invention enables reduced active levels, and therefore
reduced potential for retinoid dermatitis, while retaining
significant positive skin conditioning benefits. In addition,
higher levels of retinoid may still be used to obtain greater skin
conditioning efficacy, without undesirable retinoid dermatitis
occurring.
As used herein, "retinoid" includes all natural and/or synthetic
analogs of Vitamin A or retinol-like compounds which possess the
biological activity of Vitamin A in the skin as well as the
geometric isomers and stereoisomers of these compounds. The
retinoid is preferably retinol, retinol esters (e.g., C.sub.2
-C.sub.22 alkyl esters of retinol, including retinyl palmitate,
retinyl acetate, retinyl propionate), retinal, and/or retinoic acid
(including all-trans retinoic acid and/or 13-cis-retinoic acid),
more preferably retinoids other than retinoic acid. These compounds
are well known in the art and are commercially available from a
number of sources, e.g., Sigma Chemical Company (St. Louis, Mo.),
and Boerhinger Mannheim (Indianapolis, Ind.). Other retinoids which
are useful herein are described in U.S. Pat. No. 4,677,120, issued
Jun. 30, 1987 to Parish et al.; U.S. Pat. No. 4,885,311, issued
Dec. 5, 1989 to Parish et al.; U.S. Pat. No. 5,049,584, issued Sep.
17, 1991 to Purcell et al.; U.S. Pat. No. 5,124,356, issued Jun.
23, 1992 to Purcell et al.; and Reissue Pat. No. 34,075, issued
Sep. 22, 1992 to Purcell et al. Other suitable retinoids are
tocopheryl-retinoate [tocopherol ester of retinoic acid (trans- or
cis-), adapalene {6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic
acid}, and tazarotene (ethyl
6-[2-(4,4-dimethylthiochroman-6-yl)-ethynyl]nicotinate). One or
more retinoids may be used herein. Preferred retinoids are retinol,
retinyl palmitate, retinyl acetate, retinyl proprionate, retinal
and combinations thereof. More preferred are retinol and retinyl
propionate.
The retinoid may be included as the substantially pure material, or
as an extract obtained by suitable physical and/or chemical
isolation from natural (e.g., plant) sources. The retinoid is
preferably substantially pure, more preferably essentially
pure.
The compositions of this invention may contain a safe and effective
amount of the retinoid, such that the resultant composition is safe
and effective for regulating skin condition, preferably for
regulating visible and/or tactile discontinuities in skin, more
preferably for regulating signs of skin aging, even more preferably
for regulating visible and/or tactile discontinuities in skin
texture associated with skin aging. The compositions preferably
contain from or about 0.005% to or about 2%, more preferably 0.01%
to or about 2%, retinoid. Retinol is most preferably used in an
amount of from or about 0.01% to or about 0.15%; retinol esters are
most preferably used in an amount of from or about 0.01% to or
about 2% (e.g., about 1%); retinoic acids are most preferably used
in an amount of frorm or about 0.01% to or about 0.25%;
tocopheryl-retinoate [tocopherol ester of retinoic acid (trans- or
cis), adapalene {6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic
acid}, and tazarotene are most preferably used in an amount of from
or about 0.01% to or about 2%. When the composition contains a
retinoid, the vitamin B.sub.3 compound is preferably used in an
amount of from or about 0.1% to or about 10%, more preferably from
or about 2% to or about 5%.
C. Antimicrobial Agents
As used herein, "antimicrobial agent" means a compound capable of
destroying microbes, preventing the development of microbes or
preventing the pathogenic action of microbes. Antimicrobial agents
are useful, for example, in controlling acne. A safe and effective
amount of an antimicrobial agent may be added to compositions of
the subject invention, preferably from about 0.001% to about 10%,
more preferably from about 0.01% to about 5%, also from about 0.05%
to about 2% or from about 0.05% to about 1% of the compositions.
Preferred antimicrobial agents useful in the subject invention are
benzoyl peroxide, erythromycin, tetracycline, clindamycin, azelaic
acid, and sulfur resorcinol.
D. Antiandrogens
As used herein, "anti-androgen" means a compound capable of
correcting androgen-related disorders by interfering with the
action of androgens at their target organs. The target organ for
the subject invention is mammalian skin. Exemplary antiandrogens
include pregnenalone (and its derivatives), hops extract,
oxygenated alkyl substituted bicyclo alkanes (e.g.,
ethoxyhexyl-bicyclo octanones such as marketed by Chantal
Pharmaceutical of Los Angeles, Calif. under the trade names ETHOCYN
and CYOCTOL, and 2-(5-ethoxy hept-1-yl)bicylo[3.3.0]octanone), and
oleanolic acid. Suitable antiandrogens are disclosed in U.S. Pat.
Nos. 4,689,345 and 4,855,322, both issued to Kasha et al. on Aug.
25, 1987 and Aug. 8, 1989, respectively, each incorporated herein
by reference.
E. Sunscreens and Sunblocks
Exposure to ultraviolet light can result in excessive scaling and
texture changes of the stratum corneum. Therefore, the compositions
of the subject invention preferably contain a sunscreen or
sunblock. Suitable sunscreens or sunblocks may be organic or
inorganic.
A wide variety of conventional sunscreening agents are suitable for
use herein. Sagarin, et al., at Chapter VIII, pages 189 et seq., of
Cosmetics Science and Technology (1972), discloses numerous
suitable agents, and is incorporated herein by reference. Specific
suitable sunscreening agents include, for example: p-aminobenzoic
acid, its salts and its derivatives (ethyl, isobutyl, glyceryl
esters; p-dimethylaminobenzoic acid); anthranilates (i.e.,
o-amino-benzoates; methyl, menthyl, phenyl, benzyl, phenylethyl,
linalyl, terpinyl, and cyclohexenyl esters); salicylates (amyl,
phenyl, octyl, benzyl, menthyl, glyceryl, and di-pro-pyleneglycol
esters); cinnamic acid derivatives (menthyl and benzyl esters,
a-phenyl cinnamonitrile; butyl cinnamoyl pyruvate);
dihydroxycinnamic acid derivatives (umbelliferone,
methylumbelliferone, methylaceto-umbelliferone);
trihydroxy-cinnamic acid derivatives (esculetin, methylesculetin,
daphnetin, and the glucosides, esculin and daphnin); hydrocarbons
(diphenylbutadiene, stilbene); dibenzalacetone and
benzalacetophenone; naphtholsulfonates (sodium salts of
2-naphthol-3,6-disulfonic and of 2-naphthol-6,8-disulfonic acids);
di-hydroxynaphthoic acid and its salts; o- and
p-hydroxybiphenyldisulfonates; coumarin derivatives (7-hydroxy,
7-methyl, 3-phenyl); diazoles (2-acetyl-3-bromoindazole, phenyl
benzoxazole, methyl naphthoxazole, various aryl benzothiazoles);
quinine salts (bisulfate, sulfate, chloride, oleate, and tannate);
quinoline derivatives (8-hydroxyquinoline salts,
2-phenylquinoline); hydroxy- or methoxy-substituted benzophenones;
uric and violuric acids; tannic acid and its derivatives (e.g.,
hexaethylether); (butyl carbotol) (6-propyl piperonyl) ether;
hydroquinone; benzophenones (oxybenzene, sulisobenzone,
dioxybenzone, benzoresorcinol, 2,2',4,4'-tetrahydroxybenzophenone,
2,2'-dihydroxy-4,4'-dimethoxybenzophenone, octabenzone;
4-isopropyldibenzoylmethane; butylmethoxydibenzoylmethane;
etocrylene; octocrylene; [3-(4'-methylbenzylidene bornan-2-one) and
4-isopropyl-di-benzoylmethane.
Of these, 2-ethylhexyl-p-methoxycinnamate (commercially available
as PARSOL MCX), 4,4'-t-butyl methoxydibenzoyl-methane (commercially
available as PARSOL 1789), 2-hydroxy-4-methoxybenzophenone,
octyldimethyl-p-aminobenzoic acid, digalloyltrioleate,
2,2-dihydroxy-4-methoxybenzophenone,
ethyl-4-(bis(hydroxy-propyl))aminobenzoate,
2-ethylhexyl-2-cyano-3,3-diphenylacrylate, 2-ethylhexyl-salicylate,
glyceryl-p-aminobenzoate, 3,3,5-tri-methylcyclohexylsalicylate,
methylanthranilate, p-dimethyl-aminobenzoic acid or aminobenzoate,
2-ethylhexyl-p-dimethyl-amino-benzoate,
2-phenylbenzimidazole-5-sulfonic acid,
2-(p-dimethylaminophenyl)-5-sulfonicbenzoxazoic acid, octocrylene
and mixtures of these compounds, are preferred.
More preferred organic sunscreens useful in the compositions useful
in the subject invention are 2-ethylhexyl-p-methoxycinnamate,
butylmrethoxydibenzoylmethane, 2-hydroxy-4-methoxybenzo-phenone,
2-phenylbenzimridazole-5-sulfonic acid,
octyldimethyl-p-aminobenzoic acid, octocrylene and mixtures
thereof.
Also particularly useful in the compositions are sunscreens such as
those disclosed in U.S. Pat. No. 4,937,370 issued to Sabatelli on
Jun. 26, 1990, and U.S. Pat. No. 4,999,186 issued to Sabatelli
& Spirnak on Mar. 12, 1991, both of which are incorporated
herein by reference. The sunscreening agents disclosed therein
have, in a single molecule, two distinct chromophore moieties which
exhibit different ultra-violet radiation absorption spectra. One of
the chromophore moieties absorbs predominantly in the UVB radiation
range and the other absorbs strongly in the UVA radiation
range.
Preferred members of this class of sunscreening agents are
4-N,N-(2-ethylhexyl)methyl-aminobenzoic acid ester of
2,4-dihydroxybenzophenone; N,N-di-(2-ethylhexyl)-4-aminobenzoic
acid ester with 4-hydroxydibenzoylmethane;
4-N,N-(2-ethylhexyl)methyl-aminobenzoic acid ester with
4-hydroxydibenzoylmethane; 4-N,N-(2-ethylhexyl)methyl-aminobenzoic
acid ester of 2-hydroxy-4-(2-hydroxyethoxy)benzophenone;
4-N,N-(2-ethylhexyl)-methylaminobenzoic acid ester of
4-(2-hydroxyethoxy)dibenzoylmethane;
N,N-di-(2-ethylhexyl)-4-aminobenzoic acid ester of
2-hydroxy-4-(2-hydroxyethoxy)benzophenone; and
N,N-di-(2-ethylhexyl)-4-aminobenzoic acid ester of
4-(2-hydroxyethoxy)dibenzoylmethane and mnixtures thereof.
Suitable inorganic sunscreens or sunblocks include metal oxides,
e.g., zinc oxide and titanium dioxide. For example, the use of a
titanium dioxide in topical sunscreen compositions that is
applicable to the present invention is described in copending
application Ser. No. 08/448,942, filed on May 24, 1995, in the
names of Jiang Yue, Lisa R. Dew and Donald L. Bissett, incorporated
herein by reference.
Especially preferred sunscreens or sunblocks include the metal
oxides such as zinc oxide and titanium dioxide,
butylmethoxydibenzoylmethane, 2-ethylhexyl-p-methoxycinnamate,
phenyl benzimidazole sulfonic acid, and octocrylene.
A safe and effective amount of the sunscreen or sunblock is used,
typically from about 1% to about 20%, more typically from about 2%
to about 10%. Exact amounts will vary depending upon the sunscreen
chosen and the desired Sun Protection Factor (SPF).
An agent may also be added to any of the compositions useful in the
subject invention to improve the skin substantivity of those
compositions, particularly to enhance their resistance to being
washed off by water, or rubbed off. A preferred agent which will
provide this benefit is a copolymer of ethylene and acrylic acid.
Compositions comprising this copolymer are disclosed in U.S. Pat.
No. 4,663,157, Brock, issued May 5, 1987, which is incorporated
herein by reference.
F. Photoprotection Enhancing Agents
The compositions of the present invention may also comprise agents
which enhance the photoprotective effects of vitamin B3 compounds.
These compounds include tocopherol and tocopherol esters,
especially tocopherol sorbate; polyphenols (as present in, e.g.,
green tea extract, grape extract, bark extract, etc.), flavonoids
(e.g., flavones, isoflavones, flavonones, flavanes, chalcones,
coumarins, etc.) and derivatives such as rutin and trihydroxy ethyl
rutin; iron chelators such as 2-furildioxime, 2-furilmonoxime,
2,4,6-tri(2-pyridyl)-1,3,5-triazin, desferal, and chelator L1
(1,2-dimethyl-3-hydroxy-pyrid-4-one); anti-inflammatory agents such
as ibuprofen, naproxen, flufenamic acid, etofenamate, aspirin and
the like. A mechanism by which photodamage occurs in skin is by
oxidative damage (oxidative stress) to epidermal and dermal cells,
whose function is then impaired (e.g., elastosis which is dermal
cell over-production of abnormal elastin). Vitamin B.sub.3
compounds such as niacinamide serve as precursors to such enzyme
co-factors as nicotinamide adenine nucleotide (NAD) and
nicotinamide adenine dinucleotide phosphate (NADP) and their
reduced forms (NADH and NADPH). These co-factors are essential for
maintaining the cell's energy balance or reducing capacity (i.e.,
the production and/or maintenance of anti-oxidizing substances such
as superoxide dismutase, catalase, glutathione, tocopherol, etc.).
Without being limited by theory, it is believed that increased
levels of these co-factors (and/or their precursors) improve the
reducing capacity of cells and, hence, aid in neutralizing and
reducing the oxidative stress associated with these free radicals.
The above listed groups of photoprotection agents function by a
different mechanism, inhibiting photodamage at other steps in the
damage process. For example, tocopherol compounds, polyphenols,
flavonoids, and iron chelators prevent formation of or react with
oxygen radicals and thus prevent radical damage to cells.
Anti-inflammatory agents prevent the release of oxygen radicals and
degradative enzymes from inflammatory cells that can damage
epidermal and dermal cells and thus also prevent damage to cells.
By combining photoprotection enhancing agents with vitamin B.sub.3
compounds, the photoprotective effect of vitamin B.sub.3 compounds
is, thus, improved.
G. Anti-Oxidants/Radical Scavengers
Preferred compositions of the subject invention include an
anti-oxidant/radical scavenger as an active in addition to the
primary active agents. The anti-oxidant/radical scavenger is
especially useful for providing protection against UV radiation
which can cause increased scaling or texture changes in the stratum
corneum and against other environmental agents which can cause skin
damage.
A safe and effective amount of an anti-oxidant/radical scavenger
may be added to the compositions of the subject invention,
preferably from about 0.1% to about 10%, more preferably from about
1% to about 5%, of the composition.
Anti-oxidants/radical scavengers such as ascorbic acid (vitamin C)
and its salts, ascorbyl esters of fatty acids, ascorbic acid
derivatives (e.g., magnesium ascorbyl phosphate), tocopherol
(vitamin E), tocopherol sorbate, other esters of tocopherol,
butylated hydroxy benzoic acids and their salts,
6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid
(commercially available under the tradename Trolox.sup.R), gallic
acid and its alkyl esters, especially propyl gallate, uric acid and
its salts and alkyl esters, sorbic acid and its salts, amines
(e.g., N,N-diethylhydroxylamine, amino-guanidine), sulfhydryl
compounds (e.g., glutathione), dihydroxy fumaric acid and its
salts, lycine pidolate, arginine pilolate, nordihydroguaiaretic
acid, bioflavonoids, lysine, methionine, proline, superoxide
dismutase, silymarin, tea extracts, grape skin/seed extracts,
melanin, and rosemary extracts may be used. Preferred
anti-oxidants/radical scavengers are selected from tocopherol
sorbate and other esters of tocopherol, more preferably tocopherol
sorbate. For example, the use of tocopherol sorbate in topical
compositions and applicable to the present invention is described
in U.S. Pat. No. 4,847,071, issued on Jul. 11, 1989 to Donald L.
Bissett, Rodney D. Bush and Ranjit Chatterjee, incorporated herein
by reference.
H. Chelators
As used herein, "chelating agent" means an active agent capable of
removing a metal ion from a system by forming a complex so that the
metal ion cannot readily participate in or catalyze chemical
reactions. The inclusion of a chelating agent is especially useful
for providing protection against UV radiation which can contribute
to excessive scaling or skin texture changes and against other
environmental agents which can cause skin damage.
A safe and effective amount of a chelating agent may be added to
the compositions of the subject invention, preferably from about
0.1% to about 10%, more preferably from about 1% to about 5%, of
the composition. Exemplary chelators that are useful herein are
disclosed in U.S. Pat. No. 5,487,884, issued Jan. 30, 1996 to
Bissett et al.; International Publication No. 91/16035, Bush et
al., published Oct. 31, 1995; and International Publication No.
91/16034, Bush et al., published Oct. 31, 1995; all incorporated
herein by reference. Preferred chelators useful in compositions of
the subject invention are fiurildioxime, finrilmonoxime, and
derivatives thereof.
I. Organic Hydroxy Acids
Compositions of the present invention preferably comprise an
organic hydroxy acid. Suitable hydroxy acids include C.sub.1
-C.sub.18 hydroxy acids, preferably C.sub.8 or below. The hydroxy
acids can be substituted or unsubstituted, straight chain, branched
chain or cyclic (preferably straight chain), and saturated or
unsaturated (mono- or poly-unsaturated) (preferably saturated).
Non-limiting examples of suitable hydroxy acids include salicylic
acid, glycolic acid, lactic acid, 5 octanoyl salicylic acid,
hydroxyoctanoic acid, hydroxycaprylic acid, and lanolin fatty
acids. Preferred concentrations of the organic hydroxy acid range
from about 0.1% to about 10%, more preferably from about 0.2% to
about 5%, also preferably from about 0.5% to about 2%. Salicylic
acid is preferred. The organic hydroxy acids enhance the skin
appearance benefits of the present invention. For example, the
organic hydroxy acids tend to improve the texture of the skin.
J. Desquamation Agents/Exfoliants
A safe and effective amount of a desquamation agent is preferably
added to the compositions of the subject invention, more preferably
from about 0.1% to about 10%, even more preferably from about 0.2%
to about 5%, also preferably from about 0.5% to about 4% of the
composition. Desquamation agents enhance the skin appearance
benefits of the present invention. For example, the desquamation
agents tend to improve the texture of the skin (e.g., smoothness).
A variety of desquamation agents are known in the art and are
suitable for use herein, including but not limited to the organic
hydroxy agents described above. One desquamation system that is
suitable for use herein comprises sulfhydryl compounds and
zwitterionic surfactants and is described in copending application
Ser. No. 08/480,632, filed on Jun. 7, 1995 in the name of Donald L.
Bissett, corresponding to PCT Application No. U.S. Ser. No.
95/08136, filed Jun. 29, 1995, each incorporated herein by
reference. Another desquamation system that is suitable for use
herein comprises salicylic acid and zwitterionic surfactants and is
described in copending patent application Ser. No. 08/554,944,
filed on Nov. 13, 1995 as a continuation of Ser. No. 08/209,401,
filed on Mar. 9, 1994 in the name of Bissett, corresponding to PCT
Application No. 94/12745, filed Nov. 4, 1994, published May 18,
1995, each incorporated herein by reference. Zwitterionic
surfactants such as described in these applications are also useful
as desquamatory agents herein, with cetyl betaine being
particularly preferred.
K. Depilation Agents
The compositions of the present invention may include a safe and
effective amount of a depilation agent. When used, the composition
preferably contains from about 0.1% to about 10%, more preferably
from about 0.2% to about 5%, also preferably from about 0.5% to
about 2% of depilation agent. A depilation agent preferred for use
herein comprises a sulfhydryl compound, e.g., N-acetyl-L-cysteine.
The use of such depilation agents is described in more detail in
copending application Ser. No. 08/479,878, filed on Jun. 7, 1995,
in the name of Greg G. Hillebrand and Vladimir Gartstein,
corresponding to PCT Application No. U.S. Ser. No. 95/07311, filed
Jun. 8, 1995, each incorporated herein by reference.
L. Skin Lightening Agents
The compositions of the present invention may comprise a skin
lightening agent. When used, the compositions preferably comprise
from about 0.1% to about 10%, more preferably from about 0.2% to
about 5%, also preferably from about 0.5% to about 2%, of a skin
lightening agent. Suitable skin lightening agents include those
known in the art, including kojic acid, arbutin, ascorbic acid and
derivatives thereof, e.g., magnesium ascorbyl phosphate. Skin
lightening agents suitable for use herein also include those
described in copending patent application Ser. No. 08/479,935,
filed on Jun. 7, 1995 in the name of Hillebrand, corresponding to
PCT Application No. U.S. Ser. No. 95/07432, filed Jun. 12, 1995;
and copending patent application Ser. No. 08/390,152, filed on Feb.
24, 1995 in the names of Kalla L. Kvalnes, Mitchell A. DeLong,
Barton J. Bradbury, Curtis B. Motley, and John D. Carter,
corresponding to PCT Application No. U.S. Ser. No. 95/02809, filed
Mar. 1, 1995, published Sep. 8, 1995; all incorporated herein by
reference.
The vitamin B.sub.3 compounds of the present invention are also
known to provide skin lightening. See, British Patent 1,370,236 and
U.S. Pat. No. 4,096,240. The present inventors have found several
compounds which enhance the skin lightening effect of vitamin
B.sub.3 compounds. Such compounds include deoxy-arbutin and
derivatives; anti-oxident compounds such as tocopherols and
derivatives (e.g., tocopherol sorbate), and polyphenols (as present
in, e.g., green tea extract, grape extract, bark extract, etc.);
iron chelators such as 2-furildioxime, 2-furilmonoxime,
2,4,6-tri(2-pyridyl)-1,3,5-triazine, desferal, and chelator L1
(1,2-dimethyl-3-hydroxy-pyrid-4-one); and flavonoids (e.g.,
flavones, isoflavones, flavonones, flavanes, chalcones, coumarins,
etc.) and derivatives such as rutin and trihydroxy ethyl rutin; and
anti-inflammatory agents such as ibuprofen, naproxen, flufenamic
acid, etofenamate, aspirin and the like. Without being limited by
theory, these agents function by a mechanism different from
niacinamide and thus additively or synergistically control
pigmentation or melanin production. A mechanism by which
pigmentation is induced in skin is by oxidative damage (oxidative
stress) to melanocytes, which then in response produce melanin.
Vitamin B.sub.3 compounds such as niacinarnide serve as precursors
to such enzyme co-factors as nicotinamide adenine nucleotide (NAD)
and nicotinamide adenine dinucleotide phosphate (NADP) and their
reduced forms (NADH and NADPH). These co-factors are essential for
maintaining the cell's energy balance or reducing capacity (i.e.,
the production and/or maintenance of anti-oxidizing substances such
as superoxide dismutase, catalase, glutathione, tocopherol, etc.).
Without being limited by theory, it is believed that increased
levels of these co-factors (and/or their precursors) improve the
reducing capacity of cells and, hence, aid in neutralizing and
reducing the oxidative stress associated with these free radicals.
The above listed skin lightening agents function by inhibiting
various steps in the biosynthetic pathway of melanin production.
For example, deoxyarbutin inhibits the enzyme tyrosinase which is
involved in some steps of the conversion of tyrosine to melanin;
anti-oxidants, iron chelators, polyphenols, and flavonoids block
oxidative steps in the melanin production pathway; and
anti-inflammatory agents prevent the release of oxygen radicals and
degradative enzymes from inflammatory cells that can damage
melanocytes and thus stimulate melanin production. By combining
skin lightening agents with vitamin B.sub.3 compounds, the skin
lightening effect of vitamin B.sub.3 compounds is, thus,
improved.
M. Zinc Salts
The compositions of the present invention may further comprise a
zinc salt. Zinc salts are especially preferred where the
composition contains a sulfhydryl compound, e.g.,
N-acetyl-L-cysteine. Without intending to be limited or bound by
theory, it is believed that the zinc salt acts as a chelating agent
capable of complexing with the sulfhydryl compound prior to topical
application, stabilizes the sulfhydryl compound and/or controls
odor associated with the sulfhydryl compound. Concentrations of the
zinc salt can range from about 0.001% to about 10%, more preferably
from about 0.01% to about 5%, most preferably from about 0.1% to
about 0.5% by weight of the composition.
Preferred zinc salts include zinc acetate, zinc acetate hydrates
such as zinc acetate-2-water, zinc aluminum oxide complexes such as
gahnite, zinc diamine, zinc antimonide, zinc bromate hydrates such
as zinc bromate-6-water, zinc bromide, zinc carbonates such as
zincspar and smithsonite, zinc chlorate hydrates such as zinc
chlorate-4-water, zinc chloride, zinc diamine dichloride, zinc
citrate, zinc chromate, zinc dichromate, zinc diphosphate, zinc
hexacyanofluoride ferrate (II), zinc fluoride, zinc fluoride
hydrates such as zinc fluoride-4-water, zinc fornate, zinc formate
hydrates such as zinc formate-2-water, zinc hydroxide, zinc iodate,
zinc iodate hydrates such as zinc iodate-2-water, zinc iodide, zinc
iron oxide complexes, zinc nitrate hydrates such as zinc
nitrate-6-water, zinc nitride, zinc oxalate hydrates such as zinc
oxalate-2-water, zinc oxides such as zincite, zinc perchlorate
hydrates such as zinc perchlorate-6-water, zinc permanganate
hydrates such as zinc permanganate-6-water, zinc peroxide, zinc
p-phenolsulfonate hydrates such as zinc p-phenosulfonate-8-water,
zinc phosphate, zinc phosphate hydrates such as zinc
phosphate-4-water, zinc phosphide, zinc propionate, zinc selenate
hydrates such as zinc selenate-5-water, zinc selenide, zinc
silicates such as zinc silicate (2) and zinc silicate (4), zinc
silicon oxide water complexes such as hemimorphite, zinc
hexafluorosilicate hydrates such as zinc
hexafluorosilicate-6-water, zinc stearate, zinc sulfate, zinc
sulfate hydrates such as zinc sulfate-7-water, zinc sulfide, zinc
sulfite hydrates such as zinc sulfite-2-water, zinc telluride, zinc
thiocyanate, zinc (II) salts of N-acetyl L-cysteine, and mixtures
thereof.
Especially preferred zinc salts include zinc citrate, zinc oxide,
zinc chloride, zinc acetate, zinc stearate, zinc sulfate, and
mixtures thereof. Zinc citrate is especially preferred.
N. Humectants, Moisturizers and Skin Conditioners
The compositions of the present invention may further comprise a
humectant, moisturizing agent or other skin conditioning agent. A
variety of these materials can be employed and each can be present
at a level of from or about 0.1% to or about 20%, more preferably
from or about 1% to or about 10%, and most preferably from or about
2% to or about 5%. These materials include hydroscopic agents such
as guanidine and urea; alpha-hydroxy acids such as glycolic acid
and glycolate salts (e.g. ammonium and quaternary alkyl ammonium)
and lactic acid and lactate salts (e.g. ammonium and quaternary
alkyl ammonium) and the like; alpha-keto acids such as pyruvic acid
and the like; pyrrolidone carboxylic acid; betaine; amino acids
such as serine and alanine and the like; aloe vera in any of its
variety of forms (e.g., aloe vera gel); polyhydroxy alcohols such
as sorbitol, mannitol, glycerol, glycerol monopropoxylate,
diglycerol, triglycerol, butanetriol, hexanetriol, propylene
glycol, butylene glycol, hexylene glycol and the like; polyethylene
glycols; sugars and starches; sugar and starch derivatives such as
glucose, fructose, and alkoxylated glucose; hyaluronic acid;
lactamide monoethanolamine; acetamide monoethanolamine; sucrose
polyesters of fatty acids (e.g., sucrose polycottonseedate);
petrolatum; silicones; lanolin and lanolin esters; methyl
isosterate and ethyl isostearate; cetyl ricinoleate; sterols (e.g.,
cholesterol); free fatty acids (e.g., C6-C22); C.sub.1 -C.sub.22
triglycerides and natural precursors (e.g., soy bean); C.sub.1
-C.sub.22 alkyl zwitterionic surfactants (e.g., Lonzaine 16SP from
Lonza Chemical Co.); lipophilic calcium chelators such as salicylic
acid and derivatives; panthenol and derivatives; salts thereof and
mixtures thereof.
Also useful herein are the propoxylated glycerols described in U.S.
Pat. No. 4,976,953, which is description is incorporated herein by
reference.
Also useful are various C1-C30 monoesters and polyesters of sugars
and related materials. These esters are derived from a sugar or
polyol moiety and one or more carboxylic acid moieties. Depending
on the constituent acid and sugar, these esters can be in either
liquid or solid form at room temperature. Examples of liquid esters
include: glucose tetraoleate, the glucose tetraesters of soybean
oil fatty acids (unsaturated), the mannose tetraesters of mixed
soybean oil fatty acids, the galactose tetraesters of oleic acid,
the arabinose tetraesters of linoleic acid, xylose tetralinoleate,
galactose pentaoleate, sorbitol tetraoleate, the sorbitol
hexaesters of unsaturated soybean oil fatty acids, xylitol
pentaoleate, sucrose tetraoleate, sucrose pentaoletate, sucrose
hexaoleate, sucrose hepatoleate, sucrose octaoleate, and mixtures
thereof. Examples of solid esters include: sorbitol hexaester in
which the carboxylic acid ester moieties are palmitoleate and
arachidate in a 1 :2 molar ratio; the octaester of raffinose in
which the carboxylic acid ester moieties are linoleate and behenate
in a 1:3 molar ratio; the heptaester of maltose wherein the
esterifying carboxylic acid moieties are sunflower seed oil fatty
acids and lignocerate in a 3:4 molar ratio; the octaester of
sucrose wherein the esterifying carboxylic acid moieties are oleate
and behenate in a 2:6 molar ratio; and the octaester of sucrose
wherein the esterifying carboxylic acid moieties are laurate,
linoleate and behenate in a 1:3:4 molar ratio. A preferred solid
material is sucrose polyester in which the degree of esterification
is 7-8, and in which the fatty acid moieties are C18 mono- and/or
di-unsaturated and behenic, in a molar ratio of unsaturates:behenic
of 1:7 to 3:5. A particularly preferred solid sugar polyester is
the octaester of sucrose in which there are about 7 behenic fatty
acid moieties and about 1 oleic acid moiety in the molecule. The
ester materials are further described in, U.S. Pat. No. 2,831,854,
U.S. Pat. No. 4,005,196, to Jandacek, issued Jan. 25, 1977; U.S.
Pat. No. 4,005,195, to Jandacek, issued Jan. 25, 1977, U.S. Pat.
No. 5,306,516, to Letton et al., issued Apr. 26, 1994; U.S. Pat.
No. 5,306,515, to Letton et al., issued Apr. 26, 1994; U.S. Pat.
No. 5,305,514, to Letton et al., issued Apr. 26, 1994; U.S. Pat.
No. 4,797,300, to Jandacek et al., issued Jan. 10, 1989; U.S. Pat.
No. 3,963,699, to Rizzi et al, issued Jun. 15, 1976; U.S. Pat. No.
4,518,772, to Volpenhein, issued May 21, 1985; and U.S. Pat. No.
4,517,360, to Volpenhein, issued May 21, 1985; all of which are
incorporated by reference herein in their entirety.
O. Other Optional Components
The compositions of the present invention may also include an
extract obtained by suitable physical and/or chemical isolation
from natural sources (e.g., plants, fungi, by-products of
microorganisms), including those known in the topical personal care
art. Preferred extracts are those which enhance the skin appearance
benefits of the present invention, and which are preferably used in
a safe and effective amount, more preferably an amount of from 0.1%
to about 20%, even more preferably 0.5% to about 10%, also from 1%
to about 5%. Such extracts include plant and fungal extracts such
as extracts of yeast, rice bran, and of the plant Centella
Asiatica. Natural extracts of Centella Asiatica are preferred and
are commercially available from MMP, Inc. of Plainfield, N.J. under
the trade name(s) Centella Asiatica E.P.C.A. ("Extract Purified of
Centella asiatica") and Genines amel. Genines amel is the purer
form of the extract.
Compounds which are known to stimulate the production of collagen
can also be used in the present invention. Such compounds include
estrogens (e.g., estradiol, estriol, estrone) and estrogen mimics,
vitamin D and precursors or derivatives (e.g., ergosterol,
7-dehydrocholesterol, vitamin D2, vitamin D3, calcitriol,
calcipotriene, etc.), Factor X (kinetin), Factor Z (zeatin),
n-methyl taurine, dipalmitoyl hydroxyproline, palrmitoyl hydroxy
wheat protein, biopeptide CL, (palmitoyl glycylhistidyl-lysine),
ASC III (Amplifier of Synthesis of Collagen III, E. Merck,
Germany), and beta glucan.
The compositions hereof can also include natural ceramides or the
like, for example, ceramide 1-6.
The compositions can also contain an oil absorbent such as are
known in the art, e.g. clays (e.g. bentonite) and polymeric
absorbents (e.g., MICROSPONGES 5647 and POLYTRAP, both commercially
available from Advanced Polymer Systems, Inc. of Redwood City,
Calif., USA. MICROSPONGES 5647 is a polymer mixture derived from
styrene, methyl methacrylate, and hydrogel
acrylate/methacrylate.
Other examples of additional components useful herein include the
following: water-soluble vitamins and derivatives thereof [e.g.,
vitamin C]; polyethyleneglycols and polypropyleneglycols; polymers
for aiding the film-forming properties and substantivity of the
composition (such as a copolymer of eicosene and vinyl pyrrolidone,
an example of which is available from GAF Chemical Corporation as
Ganex.RTM. V-220). Also useful are crosslinked and noncrosslinked
nonionic and cationic polyacrylamides [e.g., Salcare SC92 which has
the CTFA designation polyquaternium 32 (and) mineral oil, and
Salcare SC 95 which has the CTFA designation polyquaternium 37
(and) mineral oil (and) PPG-1 trideceth-6, and the nonionic
Seppi-Gel polyacrylamides available from Seppic Corp.]. Also useful
are crosslinked and uncrosslinked carboxylic acid polymers and
copolymers such as those containing one or more monomers derived
from acrylic acid, substituted acrylic acids, and salts and esters
of these acrylic acids and the substituted acrylic acids, wherein
the crosslinking agent contains two or more carbon-carbon double
bonds and is derived from a polyhydric alcohol (examples useful
herein include the carbomers, which are homopolymers of acrylic
acid crosslinked with allyl ethers of sucrose or pentaerytritol and
which are available as the Carbopol.RTM. 900 series from B.F.
Goodrich, and copolymers of C.sub.10-30 alkyl acrylates with one or
more monomers of acrylic acid, methacrylic acid, or one of their
short chain (i.e.,C.sub.1-4 alcohol) esters, wherein the
crosslinking agent is an allyl ether of sucrose or pentaerytritol,
these copolymers being known as acrylates/C10-30 alkyl acrylate
crosspolymers and are commercially available as Carbopol.RTM. 1342,
Pemulen TR-1, and Pemulen TR-2, from B.F. Goodrich). These
carboxylic acid polymers and copolymers are more fully described in
U.S. Pat. No. 5,087,4415, to Haffey et al., issued Feb. 11, 1992;
U.S. Pat. No. 4,509,949, to Huang et al., issued Apr. 5, 1985; U.S.
Pat. No. 2,798,053, to Brown, issued Jul. 2, 1957; which are
incorporated by reference herein. See also, CTFA International
Cosmetic Ingredient Dictionary, fourth edition, 1991, pp. 12 and
80; which is also incorporated herein by reference.
Also useful herein are aesthetic components such as fragrances,
pigments, colorings, essential oils, skin sensates, astringents,
skin soothing agents, skin healing agents and the like, nonlimiting
examples of these aesthetic components include clove oil, menthol,
camphor, eucalyptus oil, eugenol, menthyl lactate, witch hazel
distillate, bisabolol, dipotassium glycyrrhizinate and the
like.
Preparation of Compositions
The compositions of the present invention are generally prepared by
conventional methods such as are known in the art of making topical
compositions. Such methods typically involve mixing of the
ingredients in one or more steps to a relatively uniform state,
with or without heating, cooling, application of vacuum, and the
like.
Methods for Regulating Skin Condition
The compositions of the present invention are useful for regulating
mammalian skin condition (especially human skin, more especially
human facial skin), including visible and/or tactile
discontinuities in skin, signs of skin aging, and visible and/or
tactile discontinuities in skin associated with skin aging
(including fine lines, wrinkles, large pores, surface roughness,
skin redness, spider vessels, pigment spots, and other texture and
color discontinuities associated with aged skin). Such regulation
includes prophylactic and therapeutic regulation.
Regulating skin condition involves topically applying to the skin a
safe and effective amount of a composition of the present
invention. The amount of the composition which is applied, the
frequency of application and the period of use will vary widely
depending upon the level of vitamin B.sub.3 compound and/or other
components of a given composition and the level of regulation
desired, e.g., in light of the level of skin aging present in the
subject and the rate of further skin aging.
In a preferred embodiment, the composition is chronically applied
to the skin. By "chronic topical application" is meant continued
topical application of the composition over an extended period
during the subject's lifetime, preferably for a period of at least
about one week, more preferably for a period of at least about one
month, even more preferably for at least about three months, even
more preferably for at least about six months, and more preferably
still for at least about one year. While benefits are obtainable
after various maximum periods of use (e.g., five, ten or twenty
years), it is preferred that chronic application continue
throughout the subject's lifetime. Typically applications would be
on the order of about once per day over such extended periods,
however application rates can vary from about once per week up to
about three times per day or more.
A wide range of quantities of the compositions of the present
invention can be employed to provide a skin appearance and/or feel
benefit. Quantities of the present compositions which are typically
applied per application are, in mg composition/cm.sup.2 skin, from
about 0. 1 mg/cm.sup.2 to about 10 mg/cm.sup.2. A particularly
useful application amount is about 1 mg/cm.sup.2 to about 2
mg/cm.sup.2.
Regulating skin condition is preferably practiced by applying a
composition in the form of a skin lotion, cream, cosmetic, or the
like which is intended to be left on the skin for some esthetic,
prophylactic, therapeutic or other benefit (i.e., a "leave-on"
composition). After applying the composition to the skin, it is
preferably left on the skin for a period of at least about 15
minutes, more preferably at least about 30 minutes, even more
preferably at least about 1 hour, most preferably for at least
several hours, e.g., up to about 12 hours.
Another approach to deliver a vitamin B3 compound to the skin is to
apply the compound by use of a patch. Such an approach is
particularly useful for problem skin areas needing more intensive
treatment. The patch can Tbe occlusive, semi-occlusive or
non-occlusive. The vitamin B3 compound composition can be contained
within the patch or be applied to the skin prior to application of
the patch. The patch can also include additional actives such as
chemical initiators for exothermic reactions such as those
described in PCT application WO 9701313 to Burkett et al.
Preferably the patch is applied (e.g., to the face) at night as a
form of night therapy.
EXAMPLES
The following examples further describe and demonstrate embodiments
within the scope of the present invention. The examples are given
solely for the purpose of illustration and are not to be construed
as limitations of the present invention, as many variations thereof
are possible without departing from the spirit and scope of the
invention.
Example 1
A skin cream is prepared by conventional methods from the following
components.
Ingredient (CTFA Name) Weight % PHASE A: Water U.S.P. 57.31
Disodium EDTA 0.13 Methyl Paraben 0.25 Glycerin 3.00 Zinc Citrate
1.00 PHASE B: Cetyl Alcohol 0.56 Stearyl Alcohol 2.03 Behenyl
Alcohol 0.22 Steareth-21 (Brij 721) 0.37 Steareth-2 (Brij 72) 1.10
Distearyldimonium chloride (Varisoft TA-100) 0.95 Propyl Paraben
0.10 Polypropylene glycol-15 stearyl ether 3.25 (Arlamol E) PHASE
C: Polypropylene glycol-15 stearyl ether 2.17 (Arlamol E) titanium
dioxide 0.75 PHASE D: Niacinamide 5.00 Citric acid 0.19 water
U.S.P. 17.00 50% NaOH 0.94 PHASE E: Benzyl Alcohol 0.50 Silicone
fluid (DC Q2-1401; 0.75 cyclomethicone/dimethiconol - 50/50 blend
dimethicone 10 cst 1.00 polyethylene Low Density Beads 1.00 PHASE
F: Fragrance 0.10 PHASE G: 50% NaOH 0.33
Blend the A phase components with a suitable mixer (e.g., Tekmar
model RW20DZM), heating while stirring to a temperature of
70-80.degree. C. Separately, blend the B phase components with a
suitable mixer and heat with mixing to melt the components.
Separately, blend the C phase components and mill to obtain an
acceptably smooth mixture (e.g., using a Tekmar T50 Mill).
Add the C phase mixture to the B phase mixture and mix. Then add
the resulting mix to the A phase mixture with mixing, cool with a
cold water bath and mill, then continue stirring. Remove the
combination from the bath, with continued stirring, once the
temperature reaches 40.degree. C.
Separately, blend the D phase components by stirring until
dissolved, then add this to the combination of A-C materials.
Separately, blend the E phase components by mixing until smooth and
continuous, then add this to the combination of the A-D materials.
Add and mix the fragrance, then the NaOH. Adjust the pH as
necessary to 5.5.
Apply the composition to a subject's wrinkled, aged, or photo
damaged facial skin at the rate of 2 mg composition/cm.sup.2 skin
once or twice daily for a period of at least 3-6 months to reduce
fine lines and wrinkles and improve skiin surface texture.
Example 2
An emulsion is prepared by conventional methods from the following
components:
Ingredient Weight % Silicone fluid (Dow Corning DC 345) 15.0
Silicone fluid (Dow Corning DC 3225C) 2.5 Silicone fluid
(Goldschmidt Abil We09) 2.5 Water 71.4 Niacinamide 5.0 Tetrasodium
EDTA 0.1 Benzyl alcohol 0.3 Methyl paraben 0.2 Glycerin 3.0
Form the water phase in a suitable vessel charged with the water as
follows: add the glycerin and then niacinamide to the water with
stirring. Add to this mixture with stirring the methyl paraben
dissolved in the benzyl alcohol. Add to this mixture with stirring
the EDTA.
Form the silicone phase in a separate suitable vessel by adding and
stirring together the silicone fluids.
Add the water phase to the silicone phase slowly with stirring to
form the emulsion.
Apply the resulting composition to a subject's wrinkled, aged, or
photo damaged facial skin at the rate of 2 mg composition/cm.sup.2
skin once or twice daily for a period of at least 3-6 months to
reduce fine lines and wrinkles and improve skin surface
texture.
Example 3
A skin cream is prepared by conventional methods from the following
components.
Ingredient (CTFA Name) Weight % PHASE A: Water U.S.P. 63.96
Disodium EDTA 0.15 Glycerin 5 PHASE B: Cetyl hydroxy ethyl
cellulose 0.15 Methyl Paraben 0.25 PHASE C: Cetyl Alcohol 0.5
Stearyl Alcohol 0.5 Behenyl Alcohol 0.5 Cetyl ricinoleate 3
Steareth-2 (Brij 72) 1.05 Distearyldimonium chloride (Varisoft
TA-100) 0.25 Propyl Paraben 0.10 Myristyl myristate 1.5
Caprylic/Capritryglycerides 1.5 Mineral oil 2 Fatty acid ester of
sugar* 1 Polypropylene glycol-15 stearyl ether 1.05 (Arlamol E)
PHASE D: dimethicone 10 cst (Dow Corning) 2 PHASE E: Niacinamide 5
Water U.S.P. 10 PHASE F: Benzyl Alcohol 0.5 PHASE G: 50% NaOH 0.04
*C1-C30 monoester or polyester of sugars and one or more carboxylic
acid moieties as described herein, preferably a sucrose polyester
in which the degree of esterification is 7-8, and in which the
fatty acid moieties are C18 mono- and/or di-unsaturated and
behenic, in a molar ratio of unsaturates:behenic of 1:7 to 3:5,
more preferably the octaester of sucrose in which there are about 7
behenic fatty acids moieties and about 1 oleic acid moiety in the
molecule, e.g., # sucrose ester of cottonseed oil fatty acids.
Blend the A phase components with a suitable mixer (e.g., Tekmar
model RW20DZM), heating while stirring to a temperature of about
70-80.degree. C. Add the cetyl hyroxy ethyl cellulose and methyl
paraben with mixing at about 70-80.degree. C. to melt the
components. Separately, blend the C phase components and mill to
obtain an acceptably smooth mixture (e.g., using a Tekmar T50
Mill).
Add the C phase mixture to the above mixture and mix. Remove the
combination from the bath, with continued stirring, once the
temperature reaches about 45.degree. C. Add the dimethicone and
mix.
Separately, blend the E phase components by mixing until smooth and
continuous, then add this to the above mixture. Add and mix in the
benzyl alcohol, then the NaOH. Adjust the pH as necessary to 7.
Apply the composition to a subject's wrinkled, aged, or photo
damaged facial skin at the rate of 2 mg composition/cm.sup.2 skin
once or twice daily for a period of at least 3-6 months to reduce
fine lines and wrinkles and improve skin surface texture.
Example 4
A skin cream is prepared by conventional methods from the following
components.
Component Weight % PHASE A: benzyl alcohol 0.30 methyl
p-hydroxybenzoate (a.k.a. 0.20 methylparaben) ethanol 3.00 PHASE B:
water 60.60-61.35 disodium EDTA 0.50 glycerol 10.00 hexylene glycol
2.00 niacinamide 2.00 triethanol amine 0.05 butylated
hydroxytoluene 0.10 PHASE C: Dow Corning 345 Fluid 12.50 Abil WE-09
2.50 Dow Corning -3225C 2.50 petrolatum 1.50 retinol (10% in
soybean oil) 0.75-1.50 fatty acid ester of sugar* 1.00 *See Example
3
Blend the A phase components with a suitable mixer (e.g., Tekmar
model RW20DZM). Blend the B phase components into the A phase with
a suitable mixer. Separately, blend the C phase components until
they are uniform. Add the C phase mixture to the A/B phase mixture,
mix until uniform and emulsified, and then mill to obtain an
acceptably smooth mixture (e.g., using a Tekmar T50 Mill).
Apply the composition to a subject's wrinkled, intrinsically aged,
or photo damaged facial skin at the rate of 2 mg
composition/cm.sup.2 skin once or twice daily for a period of at
least 3-6 months to improve skin surface texture, including
diminishing fine lines and wrinkles.
An alternative skin cream having reduced retinol levels can be
prepared in the same manner from the above components wherein the
retinol is added in an amount of 0.025% (0.25% of 10% retinol in
soybean oil), quo sine to 100% with water, the amounts of the other
components being as shown.
While particular embodiments of the subject invention have been
described, it will be obvious to those skilled in the art that
various changes and modifications to the subject invention can be
made without departing from the spirit and scope of the invention.
It is intended to cover, in the appended claims, all such
modifications that are within the scope of the subject
invention.
* * * * *